WO2023139253A1

WO2023139253A1 - Antigen recognizing construct that binds specific peptide with determinable affinity and t cell receptor having antigenic specificity for kk-lc-1 as well as corresponding nucleic acid sequence, vector, host cell, pharmaceutical composition and kit

Info

Publication number: WO2023139253A1
Application number: PCT/EP2023/051516
Authority: WO
Inventors: Lucia Poncette; Oduro JENNIFER; Elisa Kieback
Original assignee: T-Knife Gmbh
Priority date: 2022-01-21
Filing date: 2023-01-23
Publication date: 2023-07-27

Abstract

The present invention inter alia relates to an antigen recognizing construct that binds to specific peptide with determinable affinity, a T cell receptor having antigenic specificity for KK-LC-1, a nucleic acid sequence encoding said antigen recognizing construct or T cell receptor, a vector comprising said nucleic acid sequence, and a host cell comprising said antigen recognizing construct or T cell receptor. The invention also relates to the antigen recognizing construct or T cell receptor, the nucleic acid sequence, the vector or the host cell for use in medicine or for use in the prevention and/or treatment of a disease. Additionally, the present invention relates to a method of treating a disease as well as a pharmaceutical composition and a respective kit, to peptides, which are able to form a complex with MHC molecules and respective ex vivo complexes.

Description

ANTIGEN RECOGNIZING CONSTRUCT THAT BINDS SPECIFIC PEPTIDE WITH DETERMINABLE AFFINITY AND

T CELL RECEPTOR HAVING ANTIGENIC SPECIFICITY FOR KK-LC-1 AS WELL AS CORRESPONDING NUCLEIC ACID SEQUENCE, VECTOR, HOST CELL, PHARMACEUTICAL COMPOSITION AND KIT

CROSS-REFERENCE TO RELATED APPLICATIONS

[001] The present application claims the benefit of priority of European Patent Application No. 22152783.1, filed January 21 , 2022, the content of which is hereby incorporated by reference it its entirety for all purposes.

FIELD OF THE INVENTION

[002] The present invention relates to an antigen recognizing construct that binds specific peptide selected from the group consisting of any one of SEQ ID NOs: 1-16 with determinable affinity, a T cell receptor (TCR) having antigenic specificity for KK-LC-1 , a nucleic acid sequence encoding said antigen recognizing construct or said T cell receptor, a respective vector comprising the nucleic acid sequence and a host cell comprising the antigen recognizing construct or the T cell receptor. The present invention further relates to an isolated peptide, wherein the peptide is able to form a complex with a Major Histocompatibility Complex (MHC) II molecule and an isolated, ex vivo complex comprising said peptide and an MHC II molecule. The invention also relates to the antigen recognizing construct or the T cell receptor, the peptide, the complex, the nucleic acid sequence, the vector, or the host cell, for use in medicine or for use in the prevention and/or treatment of a disease. The present invention further relates to a use of the antigen recognizing construct or the T cell receptor, the peptide, the complex, the nucleic acid sequence, the vector, or the host cell, for the manufacture of a medicament for treating a disease. The present invention also relates to a method of treating a disease, comprising the step of administering a therapeutically effective amount of the antigen recognizing construct or the T cell receptor, the peptide, the complex, the nucleic acid sequence, the vector, or the host cell. Additionally, the present invention also relates to a respective pharmaceutical composition and further to a respective kit for use in medicine. BACKGROUND OF THE INVENTION

[003] T cells are a key part of the cellular arm of the immune system. They specifically recognise peptide fragments that are derived from intracellular proteins and presented in complex with Major Histocompatibility Complex (MHC) molecules on the surface of antigen presenting cells (APCs). In humans, MHC molecules are known as human leukocyte antigens (HLA). MHC molecules have a binding groove in which the peptide fragments bind. Recognition of particular peptide-MHC antigens is mediated by a corresponding T cell receptor (TCR). Tumour cells express various tumour associated antigens (TAA) and peptides derived from these antigens may be displayed on the tumour cell surface. Detection of a MHC class l-presented TAA-derived peptide by a CD8+ T cell bearing the corresponding T cell receptor, leads to targeted killing of the tumour cell. However, as a consequence of the selection processes, which occur during T cell maturation in the thymus, there is a scarcity of T cells (and TCRs) in the circulating repertoire, which recognise TAA-derived peptides with a sufficiently high level of affinity. Therefore tumour cells often escape detection.

[004] It is therefore desirable to provide peptides derived from TAAs with a suitable therapeutic window, based on RNA expression, MHC complexes thereof and binding moieties that can be used for the development of new cancer therapies. Furthermore, it is desirable that said peptides are not identical to, or highly similar to, any other MHC restricted peptide, derived from an alternative protein(s), and presented by MHC on the surface of non-cancerous cells. The existence of such peptide mimics increases the risk of in vivo toxicity for targeted cancer therapies.

[005] KK-LC-1 (also known as Kita-kyushu lung cancer antigen 1, CT83 or CXorf61, and having Uniprot. accession number: Q5H943) is a membrane protein with expression mainly limited to testis. Expression has also been detected in cancer cells (for example, see Fukuyama et al., Cancer Res. 66: 4922-4928 (2006); and WO 2015/014375). Therefore, KK-LC-1 is a particularly attractive target for therapeutic interventions.

[006] There is thus a need for novel antigen recognizing constructs for the treatment of various cancers including non-small cell lung cancer (adenocarcinoma and squamous) and oesophageal cancer considering KK-LC-1 as target. Accordingly, it is an object of the invention to provide such constructs. SUMMARY OF THE INVENTION

[007] This object is inter alia accomplished by the antigen recognizing constructs, the T cell receptors, peptides, complexes, nucleic acids, vectors, host cells, compositions, and kits having the features of the respective independent claims.

[008] In a first aspect, the invention provides an antigen recognizing construct that binds a peptide selected from the group consisting of

SEQ ID NO: 1 (KLVELEHTLLSKGF), SEQ ID NO: 2 (KLVELEHTLLSKG),

SEQ ID NO: 3 (NKLVELEHTLLSK), SEQ ID NO: 4 (LVELEHTLLSKGF),

SEQ ID NO: 5 (NKLVELEHTLLSKG), SEQ ID NO: 6 (LVELEHTLLSKGFR),

SEQ ID NO: 7 (ENKLVELEHTLLSK), SEQ ID NO: 8 (NKLVELEHTLLSKGF),

SEQ ID NO: 9 (KLVELEHTLLSKGFR), SEQ ID NO: 10 (ENKLVELEHTLLSKG),

SEQ ID NO: 11 (LVELEHTLLSKGFRG), SEQ ID NO: 12 (VENKLVELEHTLLSK),

SEQ ID NO: 13 (ENKLVELEHTLLSKGF), SEQ ID NO: 14 (KLVELEHTLLSKGFRG), SEQ ID NO: 15 (VENKLVELEHTLLSKG) and SEQ ID NO: 16 (NKLVELEHTLLSKGFR) with determinable affinity.

[009] In a second aspect, the invention provides a T cell receptor (TOR) having antigenic specificity for KK-LC-1 , wherein the TOR comprises

(a) an a chain CDR1 comprising or consisting of the amino acid sequence of SEQ ID NO: 17, an a chain CDR2 comprising or consisting of the amino acid sequence of SEQ ID NO:

18, an a chain CDR3 comprising or consisting of the amino acid sequence of SEQ ID NO:

19, a p chain CDR1 comprising or consisting of the amino acid sequence of SEQ ID NO: 20, a p chain CDR2 comprising or consisting of the amino acid sequence of SEQ ID NO: 21, and a p chain CDR3 comprising or consisting of the amino acid sequence of SEQ ID NO: 22; or

(b) an a chain CDR1 comprising or consisting of the amino acid sequence of SEQ ID NO: 23, an a chain CDR2 comprising or consisting of the amino acid sequence of SEQ ID NO:

24, an a chain CDR3 comprising or consisting of the amino acid sequence of SEQ ID NO:

25, a p chain CDR1 comprising or consisting of the amino acid sequence of SEQ ID NO: 26, a p chain CDR2 comprising or consisting of the amino acid sequence of SEQ ID NO: 27, and a chain CDR3 comprising or consisting of the amino acid sequence of SEQ ID NO: 28; or

(c) an a chain CDR1 comprising or consisting of the amino acid sequence of SEQ ID NO: 29, an a chain CDR2 comprising or consisting of the amino acid sequence of SEQ ID NO:

30, an a chain CDR3 comprising or consisting of the amino acid sequence of SEQ ID NO:

31, a p chain CDR1 comprising or consisting of the amino acid sequence of SEQ ID NO: 32, a p chain CDR2 comprising or consisting of the amino acid sequence of SEQ ID NO: 33, and a p chain CDR3 comprising or consisting of the amino acid sequence of SEQ ID NO: 34; or

(d) an a chain CDR1 comprising or consisting of the amino acid sequence of SEQ ID NO: 35, an a chain CDR2 comprising or consisting of the amino acid sequence of SEQ ID NO:

36, an a chain CDR3 comprising or consisting of the amino acid sequence of SEQ ID NO:

37, a p chain CDR1 comprising or consisting of the amino acid sequence of SEQ ID NO: 38, a p chain CDR2 comprising or consisting of the amino acid sequence of SEQ ID NO: 39, and a p chain CDR3 comprising or consisting of the amino acid sequence of SEQ ID NO: 40; or

(e) an a chain CDR1 comprising or consisting of the amino acid sequence of SEQ ID NO: 41 , an a chain CDR2 comprising or consisting of the amino acid sequence of SEQ ID NO:

42, an a chain CDR3 comprising or consisting of the amino acid sequence of SEQ ID NO:

43, a p chain CDR1 comprising or consisting of the amino acid sequence of SEQ ID NO: 44, a p chain CDR2 comprising or consisting of the amino acid sequence of SEQ ID NO: 45, and a p chain CDR3 comprising or consisting of the amino acid sequence of SEQ ID NO: 46; or

(f) an a chain CDR1 comprising or consisting of the amino acid sequence of SEQ ID NO: 47, an a chain CDR2 comprising or consisting of the amino acid sequence of SEQ ID NO:

48, an a chain CDR3 comprising or consisting of the amino acid sequence of SEQ ID NO:

49, a p chain CDR1 comprising or consisting of the amino acid sequence of SEQ ID NO: 50, a p chain CDR2 comprising or consisting of the amino acid sequence of SEQ ID NO: 51, and a p chain CDR3 comprising or consisting of the amino acid sequence of SEQ ID NO: 52,

(g) an a chain CDR1 comprising or consisting of the amino acid sequence of SEQ ID NO: 53, an a chain CDR2 comprising or consisting of the amino acid sequence of SEQ ID NO:

54, an a chain CDR3 comprising or consisting of the amino acid sequence of SEQ ID NO:

55, a p chain CDR1 comprising or consisting of the amino acid sequence of SEQ ID NO: 56, a p chain CDR2 comprising or consisting of the amino acid sequence of SEQ ID NO: 57, and a p chain CDR3 comprising or consisting of the amino acid sequence of SEQ ID NO: 58, or

(h) an a chain CDR1 comprising or consisting of the amino acid sequence of SEQ ID NO: 59, an a chain CDR2 comprising or consisting of the amino acid sequence of SEQ ID NO:

60, an a chain CDR3 comprising or consisting of the amino acid sequence of SEQ ID NO:

61, a p chain CDR1 comprising or consisting of the amino acid sequence of SEQ ID NO: 62, a p chain CDR2 comprising or consisting of the amino acid sequence of SEQ ID NO: 63, and a p chain CDR3 comprising or consisting of the amino acid sequence of SEQ ID NO: 64, or (i) an a chain CDR1 comprising or consisting of the amino acid sequence of SEQ ID NO: 65, an a chain CDR2 comprising or consisting of the amino acid sequence of SEQ ID NO:

66, an a chain CDR3 comprising or consisting of the amino acid sequence of SEQ ID NO:

67, a p chain CDR1 comprising or consisting of the amino acid sequence of SEQ ID NO: 68, a p chain CDR2 comprising or consisting of the amino acid sequence of SEQ ID NO: 69, and a p chain CDR3 comprising or consisting of the amino acid sequence of SEQ ID NO: 70, or

(j) an a chain CDR1 comprising or consisting of the amino acid sequence of SEQ ID NO: 71 , an a chain CDR2 comprising or consisting of the amino acid sequence of SEQ ID NO:

72, an a chain CDR3 comprising or consisting of the amino acid sequence of SEQ ID NO:

73, a p chain CDR1 comprising or consisting of the amino acid sequence of SEQ ID NO: 74, a p chain CDR2 comprising or consisting of the amino acid sequence of SEQ ID NO: 75, and a p chain CDR3 comprising or consisting of the amino acid sequence of SEQ ID NO: 76, or

(k) an a chain CDR1 comprising or consisting of the amino acid sequence of SEQ ID NO: 77, an a chain CDR2 comprising or consisting of the amino acid sequence of SEQ ID NO:

78, an a chain CDR3 comprising or consisting of the amino acid sequence of SEQ ID NO:

79, a p chain CDR1 comprising or consisting of the amino acid sequence of SEQ ID NO: 80, a p chain CDR2 comprising or consisting of the amino acid sequence of SEQ ID NO: 81 , and a p chain CDR3 comprising or consisting of the amino acid sequence of SEQ ID NO: 82.

[0010] In a third aspect, the invention provides an isolated peptide having up to 18 amino acid residues and comprising or consisting of

(i) the amino acid sequence of any one of SEQ ID NOs: 1-16, or (ii) the amino acid sequence of any one of SEQ ID NOs: 1-16, with the exception of 1 , 2 or 3 amino acid substitution(s), and/or 1, 2 or 3 amino acid insertion(s), and/or 1 , 2 or 3 amino acid deletion(s), wherein the peptide is able to form a complex with a Major Histocompatibility Complex (MHC) II molecule.

[0011] In a fourth aspect, the invention provides an isolated, ex vivo complex comprising:

(a) a peptide having up to 18 amino acid residues and comprising or consisting of

(i) the amino acid sequence of any one of SEQ ID NOs: 1-16, or

(ii) the amino acid sequence of any one of SEQ ID NOs: 1-16, with the exception of 1, 2, or 3 amino acid substitution(s), and/or 1 , 2, or 3 amino acid insertion(s), and/or 1 , 2, or 3 amino acid deletion(s); and

(b) an MHC II molecule.

[0012] In a fifth aspect, the invention provides a nucleic acid sequence encoding an antigen recognizing construct or T cell receptor according to the first or the second aspect or a peptide according to the third aspect of the invention.

[0013] In a sixth aspect, the invention provides a vector comprising the nucleic acid sequence according to the fifth aspect of the invention.

[0014] In a seventh aspect, the invention provides a host cell comprising the antigen recognizing construct or the T cell receptor, the nucleic acid sequence, or the vector of the invention.

[0015] In an eighth aspect, the invention provides the antigen recognizing construct or the T cell receptor, the peptide, the complex, the nucleic acid sequence, the vector, or the host cell, of the invention for use in medicine or, according to the ninth aspect of the invention, for use in the prevention and/or treatment of a disease.

[0016] In a tenth aspect, the invention provides a use of the antigen recognizing construct or the T cell receptor, or the peptide, or the complex, the nucleic acid sequence, the vector, or the host cell, of the invention for the manufacture of a medicament for treating a disease.

[0017] In an eleventh aspect, the invention provides a method of treating a disease, comprising the step of administering a therapeutically effective amount of the antigen recognizing construct or the T cell receptor, or the peptide, or the complex, or the nucleic acid sequence, or the vector, or the host cell of the invention.

[0018] In a twelfth aspect, the invention provides a pharmaceutical composition comprising the antigen recognizing construct or the T cell receptor, or the peptide, or the complex, or the nucleic acid sequence, or the vector, or the host cell of the invention. [0019] In a thirteenth aspect, the invention provides a kit for use in medicine comprising the antigen recognizing construct or the T cell receptor, or the peptide, or the complex, the nucleic acid sequence, the vector, or the host cell of the invention.

[0020] In a fourteenth aspect, the invention provides a method of generating an antigen recognizing construct that binds a peptide selected from the group consisting of SEQ ID NOs: 1 to 16 with a determinable affinity, wherein the method comprises:

(i) immunization of a subject, and

(ii) isolating the antigen recognizing construct.

BRIEF DESCRIPTION OF THE DRAWINGS

[0021] The invention will be better understood with reference to the detailed description, when considered in conjunction with the non-limiting examples and the drawings, in which:

[0022] Fig. 1 shows an example of an immunization schedule, which may be applied in the method of generating an antigen recognizing construct according to the invention. ABabDR4 mice were immunized with KK-LC-1 using different methods including DNA immunization by gene gun or adenovirus as well as immunization using a pool of peptides predicted to bind to HLA-DRA/HLA-DRB1*04:01. Starting after the second immunization, CD4 T cell responses to KK-LC-1 were analyzed in the blood of immunized animals.

[0023] Fig. 2 shows a respective response received as result after an immunization step of the immunization schedule according to Fig. 1. Clear T cell responses suitable for TCR isolation were detected after the eighth immunization. This immunization schedule according to Figure 1 achieved adequate CD4 T cell responses to KK-LC-1.

[0024] Fig. 3 shows the peptide specificity of peptides 1 to 16 according to SEQ ID NOs: 1-16 (see also Table 1 as described herein). TCR transduced PBLs from two or three human donors were co-cultured with HLA-DRA/HLA-DRB1*04:01 expressing cells loaded with the different peptides (at 10'⁶ M) indicated. IFNy secretion into the culture supernatant upon activation of responsive T cells was measured by ELISA. IFNy values were normalized to IFNy values elicited against the peptide with the highest in silico- predicted affinity. Data for one representative donor is shown. TCRs are able to recognize a broad spectrum of peptides in the region of the predicted core epitope.

[0025] Fig. 4 shows the peptide sensitivity for TCRs 1 to 4 according to Table 1. TCR transduced T cells were co-cultured with HLA-DRA/HLA-DRB1*04:01 expressing cells loaded with one of the recognized peptides (KLVELEHTLLSKGF, SEQ ID NO: 1) at descending concentrations (10'⁶ M to 10'¹² M). IFNy secretion into the culture supernatant upon activation of responsive T cells was measured by ELISA. Normalized IFNy secretion curves as well as EC₅₀ values are shown for one out of three representative donors herein in Figure 4 and Table 2.

[0026] Fig. 5 shows recognition of KK-LC-1 expressing cell lines by TCRs according to the invention. TCR transduced PBLs from three human donors were co-cultured with HLA-DRA/HLA-DRB1*04:01 expressing cells transduced with KK-LC-1 (LCLwO3_KK- LC-1) or with cells expressing KK-LC-1 transduced with CIITA (to induce MHC II expression) and HLA-DRA/HLA-DRB1*04:01 (Hela_CIITA_DR4) and corresponding controls. IFNy secretion into the culture supernatant upon activation of responsive T cells was measured by ELISA. Data for one representative donor is shown. Only cells expressing both HLA-DRA/HLA-DRB1*04:01 as well as KK-LC-1 were recognized by the TCRs above background (untransduced cells).

[0027] Fig. 6 shows SEQ ID NOs: 83 to 104, which depict the a- and p-chain full-length sequences of the TCRs TCR 1 to TCR 11 of the invention. CDRs are underlined and in bold, variable regions are underlined, constant regions are in bold. The term “variable region” may also be called “variable domain” as used herein, both terms may be used synonymously. The term “constant region” may also be called “constant domain” as used herein, both terms may be used synonymously.

DETAILED DESCRIPTION OF THE INVENTION

[0028] As explained above, in a first aspect, the invention is directed to an antigen recognizing construct that binds a peptide selected from the group consisting of SEQ ID NO: 1 (KLVELEHTLLSKGF), SEQ ID NO: 2 (KLVELEHTLLSKG), SEQ ID NO: 3 (NKLVELEHTLLSK), SEQ ID NO: 4 (LVELEHTLLSKGF), SEQ ID NO: 5 (NKLVELEHTLLSKG), SEQ ID NO: 6 (LVELEHTLLSKGFR), SEQ ID NO: 7 (ENKLVELEHTLLSK), SEQ ID NO: 8 (NKLVELEHTLLSKGF), SEQ ID NO: 9 (KLVELEHTLLSKGFR), SEQ ID NO: 10 (ENKLVELEHTLLSKG), SEQ ID NO: 11 (LVELEHTLLSKGFRG), SEQ ID NO: 12 (VENKLVELEHTLLSK), SEQ ID NO: 13 (ENKLVELEHTLLSKGF), SEQ ID NO: 14 (KLVELEHTLLSKGFRG),

SEQ ID NO: 15 (VENKLVELEHTLLSKG) and SEQ ID NO: 16 (NKLVELEHTLLSKGFR) with determinable affinity.

[0029] CD4 T cells expressing the antigen recognizing construct, e.g. TCR, according to the first aspect of the invention may directly recognize cancer cells and kill them, if the cancer cells are positive for MHC class II. In addition, they may recognize tumor stromal cells, such as macrophages, which cross-present the antigen taken up from cancer cells. Reciprocal activation of the macrophage and the CD4 T cell can lead to high levels of cytokines, especially TN Fa and IFNy, which leads to destruction of blood vessels and hence destruction of the tumor.

[0030] The term “with determinable affinity” as used herein means that the antigen recognizing construct or T cell receptor according to the invention may bind the respective peptide i.e. with an affinity constant of at least 10⁴ M’¹. The term “affinity constant” as used herein means the equilibrium association constant Ka. Lower affinities, as a rule, can no longer be recorded exactly with the customary measuring methods and are therefore of minor importance for practical applications. The antigen recognizing construct or T cell receptor may, for example, bind the respective peptide with an affinity constant of at least 10⁴ M’¹, corresponding to an equilibrium dissociation constant of 100 pM. The binding affinity of the antigen recognizing construct or T cell receptor to the respective peptide can be determined by a person skilled in the art using a large number of methods, for example, using the method of fluorescence titration, using competition ELISA or using the surface plasmon resonance technique.

[0031] The antigen recognizing construct according to the first aspect of the invention may be an antibody, or fragment thereof, or a T cell receptor (TCR), or fragment thereof.

[0032] It is within the scope of the first aspect of the invention that the antigen recognizing construct is an antibody, or a fragment thereof. The term “antibody” in its various grammatical forms is used herein to refer to immunoglobulin molecules and immunologically active portions of immunoglobulin molecules, i.e., molecules that contain an antibody combining site or a paratope. Such molecules are also referred to as "antigen binding fragments" of immunoglobulin molecules. The invention further provides an antibody, or antigen binding portion thereof, which specifically binds to the antigens described herein. The antibody can be any type of immunoglobulin that is known in the art. For instance, the antibody can be of any isotype, e.g., IgA, IgD, IgE, IgG, IgM, etc. The antibody can be monoclonal or polyclonal. The antibody can be a naturally-occurring antibody, e.g., an antibody isolated and/or purified from a mammal, e.g., mouse, rabbit, goat, horse, chicken, hamster, human, etc. Alternatively, the antibody can be a genetically-engineered antibody, e.g., a humanized antibody or a chimeric antibody. The antibody can be in monomeric or polymeric form.

[0033] A "T cell" or "T lymphocyte" is an immune system cell that matures in the thymus and produces T cell receptors (TCR). T cells can be naive ("T_N"; not exposed to antigen; increased expression of CD62L, CCR7, CD28, CD3, CD127, and CD45RA, and decreased or no expression of CD45RO as compared to T_CM), memory T cells (T_M) (antigen experienced and long-lived), including stem cell memory T cells, and effector cells (antigen-experienced, cytotoxic). T_M can be further divided into subsets of central memory T cells (T_EM, expresses CD62L, CCR7, CD28, CD95, CD45RO, and CD127) and effector memory T cells (T_EM express CD45RO, decreased expression of CD62L, CCR7, CD28, and CD45RA). Effector T cells (T_E) refer to antigen-experienced CD8+ cytotoxic T lymphocytes or CD4+ T cells that express CD45RA, have decreased expression of CD62L, CCR7, and CD28 as compared to T_CM, and may be positive for granzyme and perforin. CD4+ cells influence the activity of other immune cells by releasing cytokines. CD4+ T cells can activate and suppress an adaptive immune response, and which of those two functions is induced will depend on presence of other cells and signals. T cells can be collected using known techniques, and the various subpopulations or combinations thereof can be enriched or depleted by known techniques, such as by affinity binding to antibodies, flow cytometry, or immunomagnetic selection.

[0034] "T cell receptor" (TCR) refers to an immunoglobulin superfamily member having a variable binding domain, a constant domain, a transmembrane region, and a short cytoplasmic tail; see, e.g., Janeway el al., Immunobiology: The Immune System in Health and Disease, 3rd Ed., Current Biology Publications, p. 433, 1997) capable of specifically binding to an antigen peptide bound to an MHC receptor. A TCR can be found on the surface of a cell or in soluble form and generally is comprised of a heterodimer having a and p chains (also known as TCR a and TCR p, respectively), or y and 5 chains (also known as TCRy and TCR8, respectively). A polynucleotide encoding a binding protein of this disclosure, e.g., a TCR, can be codon optimized to enhance expression in a particular host cell, such, for example, as a cell of the immune system, a hematopoietic stem cell, a T cell, a primary T cell, a T cell line, a NK cell, or a natural killer T cell (Scholten el al., Clin. Immunol. 119:135, 2006).

[0035] The antigen recognizing construct may specifically bind the peptide according to any one of SEQ ID NO: 1-16 with an EC₅₀ of less than about 1 x 10'⁸ M or of less than about 2 x 10'⁸ M or of less than about 6 x 10'⁸ M. The EC₅₀ value may be determined by the procedure as carried out in Example 3 as described herein.

[0036] The term “specifically bind(s)”, as used herein, refers to an association or union of an antigen recognizing construct (e.g., TCR receptor) to a target peptide with an affinity or K_a (i.e., an equilibrium association constant of a particular binding interaction with units of 1/M) equal to or greater than 10⁴ M'¹ (which equals the ratio of the on-rate [k_on] to the off-rate [k_Off] for this association reaction), while not significantly associating or uniting with any other molecules or components in a sample.

[0037] The antigen recognizing construct according to the first aspect of the invention has an antigenic specificity for Kita-Kyushu Lung Cancer Antigen 1 (KK-LC-1). The antigen recognizing construct may bind the peptide being presented by an MHC II molecule. For example, the MHC II molecule may be an HLA-DRA molecule or an HLA- DRB1 molecule. The HLA-A molecule may be, for example, HLA-DRA/ HLA- DRB1*04:01. An exemplary amino acid sequence of HLA-DRA and HLA-DRB1*04:01 is IPD Accession No. HLA00662 for HLA-DR4 and IPD Accession No. HLA00685 for HLA- DRB1*04:01.

[0038] There are two classes of MHC-molecules, MHC class I and MHC class II. Complexes of peptide and MHC class I are recognized by CD8-positive T-cells bearing the appropriate T-cell receptor (TCR), whereas complexes of peptide and MHC class II molecules are recognized by CD4-positive T-cells bearing the appropriate TCR. Since both types of response, CD8 and CD4 dependent, contribute jointly and synergistically to the anti-tumor effect, the identification and characterization of tumor-associated and tumor-specific antigens and corresponding T cell receptors is important in the development of cancer immunotherapies such as vaccines and cell therapies.

[0039] It is within the scope of the first aspect of the invention that the antigen recognizing construct may bind the peptide according to any one of SEQ ID NOs: 1-16 with an antigenic specificity of at least 80%.

[0040] The term “antigenic specificity” as used herein, means that the antigen recognizing construct can specifically bind to and immunologically recognize its target, e.g., KK-LC-1. It may mean the ability to recognize an antigen specifically as a unique molecular entity and distinguish it from another with exquisite precision. For example, an antigen recognizing construct may be considered to have “antigenic specificity” for its target if about 1x10⁴ to about 1x10⁵ T cells expressing the antigen recognizing construct secrete at least about 200 pg/mL or more (e.g., 200 pg/mL or more, 300 pg/mL or more, 400 pg/mL or more, 500 pg/mL or more, 600 pg/mL or more, 700 pg/mL or more, 1000 pg/mL or more, 5,000 pg/mL or more, 7,000 pg/mL or more, 10,000 pg/mL or more, 20,000 pg/mL or more, or a range defined by any two of the foregoing values) of IFNy upon co-culture with (a) antigen-negative HLA-DRA/ HLA-DRB1*04:01 target cells pulsed with a low concentration of target peptide (e.g., about 0.05 ng/mL to about 5 ng/mL, 0.05 ng/mL, 0.1 ng/mL, 0.5 ng/mL, 1 ng/mL, 5 ng/mL, or a range defined by any two of the foregoing values) or (b) antigen-negative HLA-DRA/ HLA-DRB1*04:01 target cells into which a nucleotide sequence encoding the target has been introduced such that the target cell expresses the target. Cells expressing the inventive antigen recognizing constructs may also secrete IFNy upon co-culture with antigen-negative HLA-DRA/ HLA-DRB1*04:01 target cells pulsed with higher concentrations of target peptide. [0041] Any antibody molecule that specifically binds KK-LC-1 can be used herein. The antibody molecule can, for example, be a polyclonal antibody, a monoclonal antibody, or fragments typically derived from monoclonal antibodies, such as divalent antigen binding antibody fragments, or monovalent antigen binding antibody fragments. Examples of suitable divalent antibody fragments are (Fab)₂’-fragments, divalent single-chain Fv fragments or divalent single domain camelid antibodies (also knowns as nanobodies) that can be obtained by producing such single domain camelid antibodies as fusion proteins with a linker between the two single domain camelid antibodies. Examples of suitable monovalent antibody fragments include, but are not limited to, a Fab fragment, a Fv fragment, or a single-chain Fv fragment (scFv).

[0042] Specifically, as mentioned above, the antigen recognizing construct may be a T cell receptor (TCR). Such a TCR may comprise a complementary determining region 3 (CDR3) of the a chain having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity to an amino acid sequence selected from the group consisting of SEQ ID NOs: 19, 25, 31 , 37, 43, 49, 55, 61 , 67, 73, and 79 and/or wherein the T cell receptor comprises a complementary determining region 3 (CDR3) of the 0 chain having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% sequence identity to an amino acid sequence selected from the group consisting of SEQ ID NOs: 22, 28, 34, 40, 46, 52, 58, 64, 70, 76, and 82. The T cell receptor may comprise a complementary determining region 1 (CDR1) of the a chain having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% sequence identity to an amino acid sequence selected from the group consisting of SEQ ID NOs: 17, 23, 29, 35, 41, 47, 53, 59, 65, 71 , and 77, and/or wherein the T cell receptor comprises a complementary determining region 1 (CDR1) of the 0 chain having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% sequence identity to an amino acid sequence selected from the group consisting of SEQ ID NOs: 20, 26, 32, 38, 44, 50, 56, 62, 68, 74, and 80. The T cell receptor may comprise a complementary determining region 2 (CDR2) of the a chain having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% sequence identity to an amino acid sequence selected from the group consisting of SEQ ID NOs: 18, 24, 30, 36, 42, 48, 54, 60, 66, 71 , and 78, and/or wherein the T cell receptor comprises a complementary determining region 2 (CDR2) of the 0 chain having at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98 % or at least 99% sequence identity to an amino acid sequence selected from the group consisting of SEQ ID NOs: 21, 27, 33, 39, 45, 51 , 57, 63, 69, 75, and 81.

[0043] The terms "complementarity determining region" and "CDR" are synonymous with "hypervariable region" or "HVR" and are known in the art to refer to sequences of amino acids within immunoglobulin {e.g., TCR) variable regions, which confer antigen specificity and/or binding affinity and are separated from one another in primary amino acid sequence by framework regions. In general, there are three CDRs in each TCR a- chain variable region (aCDR1 , aCDR2, aCDR3) and three CDRs in each TCR p-chain variable region (PCDR1, pCDR2, pCDR3). In TCRs, CDR3 is thought to be the main CDR responsible for recognizing processed antigen. In general, CDR1 and CDR2 interact mainly or exclusively with the MHC.

[0044] It is also comprised in the first aspect of the invention that the T cell receptor comprises a complementary determining region 3 (CDR3) of the a chain having at least 95% sequence identity to an amino acid sequence selected from the group consisting of SEQ ID NOs: 19, 25, 31, 37, 43, 49, 55, 61, 67, 73, and 79, and/or wherein the T cell receptor comprises a complementary determining region 3 (CDR3) of the p chain having at least 95% sequence identity to an amino acid sequence selected from the group consisting of SEQ ID NOs: 22, 28, 34, 40, 46, 52, 58, 64, 70, 76, and 82. The T cell receptor may comprise a complementary determining region 1 (CDR1) of the a chain having at least 95% sequence identity to an amino acid sequence selected from the group consisting of SEQ ID NOs: 17, 23, 29, 35, 41 , 47, 53, 59, 65, 71, and 77, and/or wherein the T cell receptor comprises a complementary determining region 1 (CDR1) of the p chain having at least 95% sequence identity to an amino acid sequence selected from the group consisting of SEQ ID NOs: 20, 26, 32, 38, 44, 50, 56, 62, 68, 74, and 80. The T cell receptor may comprise a complementary determining region 2 (CDR2) of the a chain having at least 95% sequence identity to an amino acid sequence selected from the group consisting of SEQ ID NOs: 18, 24, 30, 36, 42, 48, 54, 60, 66, 71, and 78, and/or wherein the T cell receptor comprises a complementary determining region 2 (CDR2) of the p chain having at least 95% sequence identity to an amino acid sequence selected from the group consisting of SEQ ID NOs: 21, 27, 33, 39, 45, 51 , 57, 63, 69, 75, and 81.

[0045] The T cell receptor according to the first aspect of the invention may comprise (a) an a chain CDR1 comprising or consisting of the amino acid sequence of SEQ ID NO: 17, an a chain CDR2 comprising or consisting of the amino acid sequence of SEQ ID NO: 18, and an a chain CDR3 comprising or consisting of the amino acid sequence of SEQ ID NO: 19; or

(b) an a chain CDR1 comprising or consisting of the amino acid sequence of SEQ ID NO: 23, an a chain CDR2 comprising or consisting of the amino acid sequence of SEQ ID NO: 24, and an a chain CDR3 comprising or consisting of the amino acid sequence of SEQ ID NO: 25; or

(c) an a chain CDR1 comprising or consisting of the amino acid sequence of SEQ ID NO: 29, an a chain CDR2 comprising or consisting of the amino acid sequence of SEQ ID NO: 30, and an a chain CDR3 comprising or consisting of the amino acid sequence of SEQ ID NO: 31; or

(d) an a chain CDR1 comprising or consisting of the amino acid sequence of SEQ ID NO: 35, an a chain CDR2 comprising or consisting of the amino acid sequence of SEQ ID NO: 36, and an a chain CDR3 comprising or consisting of the amino acid sequence of SEQ ID NO: 37; or

(e) an a chain CDR1 comprising or consisting of the amino acid sequence of SEQ ID NO: 41 , an a chain CDR2 comprising or consisting of the amino acid sequence of SEQ ID NO: 42, and an a chain CDR3 comprising or consisting of the amino acid sequence of SEQ ID NO: 43; or

(f) an a chain CDR1 comprising or consisting of the amino acid sequence of SEQ ID NO: 47, an a chain CDR2 comprising or consisting of the amino acid sequence of SEQ ID NO: 48, and an a chain CDR3 comprising or consisting of the amino acid sequence of SEQ ID NO: 49, or

(g) an a chain CDR1 comprising or consisting of the amino acid sequence of SEQ ID NO: 53, an a chain CDR2 comprising or consisting of the amino acid sequence of SEQ ID NO: 54, and an a chain CDR3 comprising or consisting of the amino acid sequence of SEQ ID NO: 55; or

(h) an a chain CDR1 comprising or consisting of the amino acid sequence of SEQ ID NO: 59, an a chain CDR2 comprising or consisting of the amino acid sequence of SEQ ID NO: 60, and an a chain CDR3 comprising or consisting of the amino acid sequence of SEQ ID NO: 61; or

(i) an a chain CDR1 comprising or consisting of the amino acid sequence of SEQ ID NO:

65, an a chain CDR2 comprising or consisting of the amino acid sequence of SEQ ID NO:

66, and an a chain CDR3 comprising or consisting of the amino acid sequence of SEQ ID NO: 67; or

(j) an a chain CDR1 comprising or consisting of the amino acid sequence of SEQ ID NO: 71 , an a chain CDR2 comprising or consisting of the amino acid sequence of SEQ ID NO: 72, and an a chain CDR3 comprising or consisting of the amino acid sequence of SEQ ID NO: 73; or

78, and an a chain CDR3 comprising or consisting of the amino acid sequence of SEQ ID NO:

79.

[0046] The T cell receptor according to the first aspect of the invention may comprise

(a) a p chain CDR1 comprising or consisting of the amino acid sequence of SEQ ID NO: 20, a p chain CDR2 comprising or consisting of the amino acid sequence of SEQ ID NO: 21, and a chain CDR3 comprising or consisting of the amino acid sequence of SEQ ID NO: 22; or

(b) a p chain CDR1 comprising or consisting of the amino acid sequence of SEQ ID NO: 26, a p chain CDR2 comprising or consisting of the amino acid sequence of SEQ ID NO: 27, and a p chain CDR3 comprising or consisting of the amino acid sequence of SEQ ID NO: 28; or

(c) a p chain CDR1 comprising or consisting of the amino acid sequence of SEQ ID NO: 32, a p chain CDR2 comprising or consisting of the amino acid sequence of SEQ ID NO: 33, and a p chain CDR3 comprising or consisting of the amino acid sequence of SEQ ID NO: 34; or

(d) a p chain CDR1 comprising or consisting of the amino acid sequence of SEQ ID NO: 38, a p chain CDR2 comprising or consisting of the amino acid sequence of SEQ ID NO: 39, and a p chain CDR3 comprising or consisting of the amino acid sequence of SEQ ID NO: 40; or

(e) a p chain CDR1 comprising or consisting of the amino acid sequence of SEQ ID NO: 44, a p chain CDR2 comprising or consisting of the amino acid sequence of SEQ ID NO: 45, and a p chain CDR3 comprising or consisting of the amino acid sequence of SEQ ID NO: 46; or

(f) a p chain CDR1 comprising or consisting of the amino acid sequence of SEQ ID NO: 50, a p chain CDR2 comprising or consisting of the amino acid sequence of SEQ ID NO: 51 , and a p chain CDR3 comprising or consisting of the amino acid sequence of SEQ ID NO: 52, or (g) a p chain CDR1 comprising or consisting of the amino acid sequence of SEQ ID NO: 56, a chain CDR2 comprising or consisting of the amino acid sequence of SEQ ID NO: 57, and a p chain CDR3 comprising or consisting of the amino acid sequence of SEQ ID NO: 58; or

(h) a p chain CDR1 comprising or consisting of the amino acid sequence of SEQ ID NO: 62, a p chain CDR2 comprising or consisting of the amino acid sequence of SEQ ID NO: 63, and a p chain CDR3 comprising or consisting of the amino acid sequence of SEQ ID NO: 64, or

(i) a p chain CDR1 comprising or consisting of the amino acid sequence of SEQ ID NO: 68, a p chain CDR2 comprising or consisting of the amino acid sequence of SEQ ID NO: 69, and a p chain CDR3 comprising or consisting of the amino acid sequence of SEQ ID NO: 70; or

(j) a p chain CDR1 comprising or consisting of the amino acid sequence of SEQ ID NO: 74, a p chain CDR2 comprising or consisting of the amino acid sequence of SEQ ID NO: 75, and a p chain CDR3 comprising or consisting of the amino acid sequence of SEQ ID NO: 76, or

(k) a p chain CDR1 comprising or consisting of the amino acid sequence of SEQ ID NO: 80, a p chain CDR2 comprising or consisting of the amino acid sequence of SEQ ID NO: 81 , and a p chain CDR3 comprising or consisting of the amino acid sequence of SEQ ID NO: 82.

[0047] The T cell receptor according to the first aspect of the invention may comprise

(a) an a chain CDR1 comprising or consisting of the amino acid sequence of SEQ ID NO: 17, an a chain CDR2 comprising or consisting of the amino acid sequence of SEQ ID NO: 18, an a chain CDR3 comprising or consisting of the amino acid sequence of SEQ ID NO: 19, a p chain CDR1 comprising or consisting of the amino acid sequence of SEQ ID NO: 20, a chain CDR2 comprising or consisting of the amino acid sequence of SEQ ID NO: 21 , and a p chain CDR3 comprising or consisting of the amino acid sequence of SEQ ID NO: 22; or

25, a p chain CDR1 comprising or consisting of the amino acid sequence of SEQ ID NO: 26, a p chain CDR2 comprising or consisting of the amino acid sequence of SEQ ID NO: 27, and a p chain CDR3 comprising or consisting of the amino acid sequence of SEQ ID NO: 28; or

37, a p chain CDR1 comprising or consisting of the amino acid sequence of SEQ ID NO: 38, a chain CDR2 comprising or consisting of the amino acid sequence of SEQ ID NO: 39, and a p chain CDR3 comprising or consisting of the amino acid sequence of SEQ ID NO: 40; or

49, a p chain CDR1 comprising or consisting of the amino acid sequence of SEQ ID NO: 50, a p chain CDR2 comprising or consisting of the amino acid sequence of SEQ ID NO: 51, and a p chain CDR3 comprising or consisting of the amino acid sequence of SEQ ID NO: 52; or

55, a p chain CDR1 comprising or consisting of the amino acid sequence of SEQ ID NO: 56, a p chain CDR2 comprising or consisting of the amino acid sequence of SEQ ID NO: 57, and a chain CDR3 comprising or consisting of the amino acid sequence of SEQ ID NO: 58, or

61, a p chain CDR1 comprising or consisting of the amino acid sequence of SEQ ID NO: 62, a p chain CDR2 comprising or consisting of the amino acid sequence of SEQ ID NO: 63, and a p chain CDR3 comprising or consisting of the amino acid sequence of SEQ ID NO: 64, or

(i) an a chain CDR1 comprising or consisting of the amino acid sequence of SEQ ID NO: 65, an a chain CDR2 comprising or consisting of the amino acid sequence of SEQ ID NO:

[0048] The T cell receptor according to the first aspect of the invention may comprise

(a) an a chain comprising CDR sequences comprising amino acid sequences of SEQ ID NOs: 17, 18, and 19, and a p chain comprising CDR sequences comprising amino acid sequences of SEQ ID NOs: 20, 21 , and 22; or

(b) an a chain comprising CDR sequences comprising amino acid sequences of SEQ ID NOs: 23, 24, and 25, and a p chain comprising CDR sequences comprising amino acid sequences of SEQ ID NOs: 26, 27, and 28; or

(c) an a chain comprising CDR sequences comprising amino acid sequences of SEQ ID NOs: 29, 30, and 31, and a p chain comprising CDR sequences comprising amino acid sequences of SEQ ID NOs: 32, 33, and 34; or

(d) an a chain comprising CDR sequences comprising amino acid sequences of SEQ ID NOs: 35, 36, and 37, and a p chain comprising CDR sequences comprising amino acid sequences of SEQ ID NOs: 38, 39, and 40; or

(e) an a chain comprising CDR sequences comprising amino acid sequences of SEQ ID NOs: 41, 42, and 43, and a p chain comprising CDR sequences comprising amino acid sequences of SEQ ID NOs: 44, 45, and 46; or

(f) an a chain comprising CDR sequences comprising amino acid sequences of SEQ ID NOs: 47, 48, and 49, and a p chain comprising CDR sequences comprising amino acid sequences of SEQ ID NOs: 50, 51, and 52; or

(g) an a chain comprising CDR sequences comprising amino acid sequences of SEQ ID NOs: 53, 54, and 55, and a p chain comprising CDR sequences comprising amino acid sequences of SEQ ID NOs: 56, 57, and 58; or (h) an a chain comprising CDR sequences comprising amino acid sequences of SEQ ID NOs: 59, 60, and 61, and a p chain comprising CDR sequences comprising amino acid sequences of SEQ ID NOs: 62, 63, and 64; or

(i) an a chain comprising CDR sequences comprising amino acid sequences of SEQ ID NOs: 65, 66, and 67, and a chain comprising CDR sequences comprising amino acid sequences of SEQ ID NOs: 68, 69, and 70; or

(j) an a chain comprising CDR sequences comprising amino acid sequences of SEQ ID NOs: 71, 72, and 73, and a p chain comprising CDR sequences comprising amino acid sequences of SEQ ID NOs: 74, 75, and 76; or

(k) an a chain comprising CDR sequences comprising amino acid sequences of SEQ ID NOs: 77, 78, and 79, and a p chain comprising CDR sequences comprising amino acid sequences of SEQ ID NOs: 80, 81, and 82.

[0049] The T cell receptor according to the first aspect of the invention may be in the form of an ap heterodimer. The T cell receptor according to the first aspect of the invention may be in a single chain format comprising said a chain and said p chain according to the invention. The T cell receptor according to the first aspect of the invention may be in a single chain format comprising any a chain sequence and any p chain sequence as depicted in Table 2 herein.

[0050] The T cell receptor according to the first aspect of the invention may comprise

(a) an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% sequence identity to the variable domain of SEQ ID NO: 83, and/or an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% sequence identity to the variable domain of SEQ ID NO: 84; or

(b) an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% sequence identity to the variable domain of SEQ ID NO: 85, and/or an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% sequence identity to the variable domain of SEQ ID NO: 86; or

(c) an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% sequence identity to the variable domain of SEQ ID NO: 87, and/or an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% sequence identity to the variable domain of SEQ ID NO: 88; or

(d) an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% sequence identity to the variable domain of SEQ ID NO: 89, and/or an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% sequence identity to the variable domain of SEQ ID NO: 90; or

(e) an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% sequence identity to the variable domain of SEQ ID NO: 91, and/or an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% sequence identity to the variable domain of SEQ ID NO: 92; or

(f) an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% sequence identity to the variable domain of SEQ ID NO: 93, and/or an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% sequence identity to the variable domain of SEQ ID NO: 94; or

(g) an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% sequence identity to the variable domain of SEQ ID NO: 95, and/or an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% sequence identity to the variable domain of SEQ ID NO: 96; or

(h) an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% sequence identity to the variable domain of SEQ ID NO: 97, and/or an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% sequence identity to the variable domain of SEQ ID NO: 98; or

(i) an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% sequence identity to the variable domain of SEQ ID NO: 99, and/or an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% sequence identity to the variable domain of SEQ ID NO: 100; or

(j) an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% sequence identity to the variable domain of SEQ ID NO: 101 , and/or an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% sequence identity to the variable domain of SEQ ID NO: 102; or

(k) an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% sequence identity to the variable domain of SEQ ID NO: 103, and/or an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% sequence identity to the variable domain of SEQ ID NO: 104. The variable domains or regions of the respective SEQ ID NOs are depicted herein in Table 2 by underlinement.

[0051] The T cell receptor according to the first aspect of the invention may comprise

(a) an a chain comprising a sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 83, and/or a p chain comprising a sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 84; or

(b) an a chain comprising a sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 85, and/or a p chain comprising a sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 86; or

(c) an a chain comprising a sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 87, and/or a p chain comprising a sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 88; or

(d) an a chain comprising a sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 89, and/or a p chain comprising a sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 90; or

(e) an a chain comprising a sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 91 , and/or a p chain comprising a sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 92; or

(f) an a chain comprising a sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 93, and/or a p chain comprising a sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 94; or

(g) an a chain comprising a sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 95, and/or a p chain comprising a sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 96; or

(h) an a chain comprising a sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 97, and/or a p chain comprising a sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 98; or

(i) an a chain comprising a sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 99, and/or a p chain comprising a sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 100; or

(j) an a chain comprising a sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 101 , and/or a p chain comprising a sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 102; or

(k) an a chain comprising a sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 103, and/or a chain comprising a sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 104.

[0052] In yet a further aspect, the invention provides a T cell receptor (TOR) having antigenic specificity for KK-LC-1 , wherein the TOR comprises:

(a) an a chain CDR1 comprising or consisting of the amino acid sequence of SEQ ID NO: 17, an a chain CDR2 comprising or consisting of the amino acid sequence of SEQ ID NO: 18, and an a chain CDR3 comprising or consisting of the amino acid sequence of SEQ ID NO: 19; or

42, and an a chain CDR3 comprising or consisting of the amino acid sequence of SEQ ID NO:

43; or

48, and an a chain CDR3 comprising or consisting of the amino acid sequence of SEQ ID NO:

49; or

54, and an a chain CDR3 comprising or consisting of the amino acid sequence of SEQ ID NO:

55; or

60, and an a chain CDR3 comprising or consisting of the amino acid sequence of SEQ ID NO:

61; or

66, and an a chain CDR3 comprising or consisting of the amino acid sequence of SEQ ID NO:

67; or

(j) an a chain CDR1 comprising or consisting of the amino acid sequence of SEQ ID NO: 71 , an a chain CDR2 comprising or consisting of the amino acid sequence of SEQ ID NO: 72, and an a chain CDR3 comprising or consisting of the amino acid sequence of SEQ ID NO:

73; or (k) an a chain CDR1 comprising or consisting of the amino acid sequence of SEQ ID NO: 77, an a chain CDR2 comprising or consisting of the amino acid sequence of SEQ ID NO:

79.

[0053] In yet a further aspect, the invention provides a T cell receptor (TCR) having antigenic specificity for KK-LC-1 , wherein the TCR comprises:

(a) a p chain CDR1 comprising or consisting of the amino acid sequence of SEQ ID NO: 20, a chain CDR2 comprising or consisting of the amino acid sequence of SEQ ID NO: 21, and a p chain CDR3 comprising or consisting of the amino acid sequence of SEQ ID NO: 22; or

(e) a p chain CDR1 comprising or consisting of the amino acid sequence of SEQ ID NO: 44, a p chain CDR2 comprising or consisting of the amino acid sequence of SEQ ID NO: 45, and a chain CDR3 comprising or consisting of the amino acid sequence of SEQ ID NO: 46; or

(f) a p chain CDR1 comprising or consisting of the amino acid sequence of SEQ ID NO: 50, a p chain CDR2 comprising or consisting of the amino acid sequence of SEQ ID NO: 51, and a p chain CDR3 comprising or consisting of the amino acid sequence of SEQ ID NO: 52; or

(g) a p chain CDR1 comprising or consisting of the amino acid sequence of SEQ ID NO: 56, a p chain CDR2 comprising or consisting of the amino acid sequence of SEQ ID NO: 57, and a p chain CDR3 comprising or consisting of the amino acid sequence of SEQ ID NO: 58; or

(j) a p chain CDR1 comprising or consisting of the amino acid sequence of SEQ ID NO: 74, a p chain CDR2 comprising or consisting of the amino acid sequence of SEQ ID NO: 75, and a p chain CDR3 comprising or consisting of the amino acid sequence of SEQ ID NO: 76; or (k) a p chain CDR1 comprising or consisting of the amino acid sequence of SEQ ID NO: 80, a chain CDR2 comprising or consisting of the amino acid sequence of SEQ ID NO: 81 , and a p chain CDR3 comprising or consisting of the amino acid sequence of SEQ ID NO: 82.

[0054] In a second aspect, the invention provides a T cell receptor (TCR) having antigenic specificity for KK-LC-1 , wherein the TCR may comprise:

(c) an a chain CDR1 comprising or consisting of the amino acid sequence of SEQ ID NO: 29, an a chain CDR2 comprising or consisting of the amino acid sequence of SEQ ID NO: 30, an a chain CDR3 comprising or consisting of the amino acid sequence of SEQ ID NO: 31, a p chain CDR1 comprising or consisting of the amino acid sequence of SEQ ID NO: 32, a chain CDR2 comprising or consisting of the amino acid sequence of SEQ ID NO: 33, and a p chain CDR3 comprising or consisting of the amino acid sequence of SEQ ID NO: 34; or

49, a p chain CDR1 comprising or consisting of the amino acid sequence of SEQ ID NO: 50, a chain CDR2 comprising or consisting of the amino acid sequence of SEQ ID NO: 51, and a p chain CDR3 comprising or consisting of the amino acid sequence of SEQ ID NO: 52; or

67, a p chain CDR1 comprising or consisting of the amino acid sequence of SEQ ID NO: 68, a p chain CDR2 comprising or consisting of the amino acid sequence of SEQ ID NO: 69, and a chain CDR3 comprising or consisting of the amino acid sequence of SEQ ID NO: 70, or

73, a p chain CDR1 comprising or consisting of the amino acid sequence of SEQ ID NO: 74, a p chain CDR2 comprising or consisting of the amino acid sequence of SEQ ID NO: 75, and a p chain CDR3 comprising or consisting of the amino acid sequence of SEQ ID NO: 76; or

[0055] In a second aspect, the invention provides a T cell receptor (TCR) having antigenic specificity for KK-LC-1 , wherein the TCR may comprise:

(a) an a chain comprising CDR sequences comprising amino acid sequences of SEQ ID NOs: 17, 18, and 19, and a p chain comprising CDR sequences comprising amino acid sequences of SEQ ID NOs: 20, 21, and 22; or

(b) an a chain comprising CDR sequences comprising amino acid sequences of SEQ ID NOs: 23, 24, and 25, and a p chain comprising CDR sequences comprising amino acid sequences of SEQ ID NOs: 26, 27, and 28; or (c) an a chain comprising CDR sequences comprising amino acid sequences of SEQ ID NOs: 29, 30, and 31, and a p chain comprising CDR sequences comprising amino acid sequences of SEQ ID NOs: 32, 33, and 34; or

(d) an a chain comprising CDR sequences comprising amino acid sequences of SEQ ID NO: 35, 36, and 37, and a chain comprising CDR sequences comprising amino acid sequences of SEQ ID NOs: 38, 39, and 40; or

(g) an a chain comprising CDR sequences comprising amino acid sequences of SEQ ID NOs: 53, 54, and 55, and a p chain comprising CDR sequences comprising amino acid sequences of SEQ ID NOs: 56, 57, and 58; or

(h) an a chain comprising CDR sequences comprising amino acid sequences of SEQ ID NOs: 59, 60, and 61, and a p chain comprising CDR sequences comprising amino acid sequences of SEQ ID NOs: 62, 63, and 64; or

(i) an a chain comprising CDR sequences comprising amino acid sequences of SEQ ID NOs: 65, 66, and 67, and a p chain comprising CDR sequences comprising amino acid sequences of SEQ ID NOs: 68, 69, and 70; or

(j) an a chain comprising CDR sequences comprising amino acid sequences of SEQ ID NOs: 71, 72, and 73, and a p chain comprising CDR sequences comprising amino acid sequences of SEQ ID NOs: 74, 75, and 75; or

[0056] In a second aspect, the invention provides a T cell receptor (TCR) having antigenic specificity for KK-LC-1 , wherein the TCR may comprise:

[0057] (k) an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% sequence identity to the variable domain of SEQ ID NO: 103, and/or an amino acid sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% sequence identity to the variable domain of SEQ ID NO: 104. The variable domains or regions of the respective SEQ ID NOs are depicted herein in Table 2 by underlinement.

[0058] In a second aspect, the invention provides a T cell receptor (TCR) having antigenic specificity for KK-LC-1 , wherein the TCR may comprise:

(k) an a chain comprising a sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 103, and/or a p chain comprising a sequence having at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 104.

[0059] Included in the scope of the invention are TCRs comprising at least one a and/or p TCR chain, wherein said a TCR chain comprises a sequence having at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to an amino acid sequence of SEQ ID NOs: 83, 85, 87, 89, 91, 93, 95, 97, 99, 101 or 103, and/or wherein said p TCR chain comprises a sequence having at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% sequence identity to an amino acid sequence of SEQ ID NOs: 84, 86, 88, 90, 92, 94, 96, 98, 100, 102 and 104.

[0060] Included in the scope of the invention are functional variants of the inventive antigen recognizing constructs or TCRs described herein. The term “functional variant”, as used herein, refers to an antigen recognizing construct or TCR having substantial or significant sequence identity or similarity to a parent antigen recognizing construct or TCR, which functional variant retains the biological activity of the antigen recognizing construct or TCR of which it is a variant. Functional variants encompass, for example, those variants of the antigen recognizing construct or TCR described herein (the parent antigen recognizing construct or TCR) that retain the ability to specifically bind to the target, e.g. KK-LC-1, for which the parent antigen recognizing construct or TCR has antigenic specificity to a similar extent, the same extent, or to a higher extent, as the parent antigen recognizing construct or TCR. In reference to the parent antigen recognizing construct or TCR, the functional variant can, for instance, be at least about 30%, 50%, 75%, 80%, 90%, 95%, 96%, 97%, 98%, 99% or more identical in amino acid sequence to the parent antigen recognizing construct or TCR.

[0061] The term "sequence identity" or "identity" as used in the present invention means the percentage of pair-wise identical residues, following homology alignment of a sequence of a polypeptide of the present invention with a sequence in question, with respect to the number of residues in the longer of these two sequences.

[0062] The percentage of sequence homology or sequence identity can, for example, be determined herein using the program BLASTP, version blastp 2.2.5 (November 16, 2002; cf. Altschul, S. F. et al. (1997) Nucl. Acids Res. 25, 3389-3402). The percentage of homology is based on the alignment of the entire polypeptide sequences (matrix: BLOSLIM 62; gap costs: 11.1; cutoff value set to 10'³) including the respective sequences. It is calculated as the percentage of numbers of "positives" (homologous amino acids) indicated as result in the BLASTP program output divided by the total number of amino acids selected by the program for the alignment.

[0063] The functional variant can, for example, comprise the amino acid sequence of the parent antigen recognizing construct or TCR with at least one conservative amino acid substitution. Conservative amino acid substitutions are known in the art, and include amino acid substitutions in which one amino acid having certain physical and/or chemical properties is exchanged for another amino acid that has the same chemical or physical properties. For instance, the conservative amino acid substitution can be an acidic amino acid substituted for another acidic amino acid (e.g., Asp or Glu), an amino acid with a non-polar side chain substituted for another amino acid with a non-polar side chain (e.g., Ala, Gly, Vai, He, Leu, Met, Phe, Pro, Trp, Vai, etc.), a basic amino acid substituted for another basic amino acid (Lys, Arg, etc.), an amino acid with a polar side chain substituted for another amino acid with a polar side chain (Asn, Cys, Gin, Ser, Thr, Tyr, etc.), etc.

[0064] The term “KK-LC-1” means Kita-Kyushu Lung Cancer antigen 1 and is e.g. deposited under the accession number UniProtKB - Q5H943.

[0065] Reverting to the aspects of the invention, in the third aspect, the invention is directed to an isolated peptide having up to 18 amino acid residues and comprising or consisting of

(i) the amino acid sequence of any one of SEQ ID NOs: 1-16, or

(ii) the amino acid sequence of any one of SEQ ID NOs: 1-16, with the exception of 1 , 2 or 3 amino acid substitution(s), and/or 1, 2 or 3 amino acid insertion(s), and/or 1 , 2 or 3 amino acid deletion(s), wherein the peptide is able to form a complex with a Major Histocompatibility Complex (MHC) II molecule. In illustrated examples, the peptide may have up to 17 amino acid residues. In another illustrated example, the peptide may consist of from 13 to 16 amino acids. In another illustrated example, the peptide may consist of an amino acid sequence of any one of SEQ ID NOs: 1-16.

[0066] Inserted amino acids and replacement amino acids may be naturally occurring amino acids or may be non-naturally occurring amino acids and, for example, may contain a non-natural side chain, and/or be linked together via non-native peptide bonds. Such altered peptide ligands are discussed further in Douat-Casassus et al., J. Med. Chem, 2007 Apr. 5; 50(7): 1598-609 and Hoppes et al., J. Immunol 2014 Nov. 15; 193(10): 4803-13 and references therein). If more than one amino acid residue is substituted and/or inserted, the replacement/inserted amino acid residues may be the same as each other or different from one another. Each replacement amino acid may have a different side chain to the amino acid being replaced. Amino acid substitutions may be conservative, by which is meant that the substituted amino acid has similar chemical properties to the original amino acid. A skilled person would understand which amino acids share similar chemical properties. For example, the following groups of amino acids share similar chemical properties such as size, charge and polarity: Group 1 = Ala, Ser, Thr, Pro, Gly; Group 2 = Asp, Asn, Glu, Gin; Group 3 = His, Arg, Lys; Group 4 = Met, Leu, He, Vai, Cys; Group 5 = Phe Thy Trp.

[0067] A peptide of the invention may be used to elicit an immune response. If this is the case, it is important that the immune response is specific to the intended target in order to avoid the risk of unwanted side effects that may be associated with an “off target” immune response. Therefore, it is preferred that the amino acid sequence of a peptide of the invention does not match the amino acid sequence of a peptide from any other protein(s), in particular, that of another human protein. A person of skill in the art would understand how to search a database of known protein sequences to ascertain whether a peptide according to the invention is present in another protein.

[0068] Peptides of the invention may be conjugated to additional moieties such as carrier molecules or adjuvants (for specific examples see Liu et al. Bioconjug Chem. 2015 May 20; 26(5): 791-801 and references therein). The peptides may be biotinylated or include a tag, such as a His tag. Examples of adjuvants used in cancer vaccines include microbes, such as the bacterium Bacillus Calmette-Guerin (BCG), and/or substances produced by bacteria, such as Detox B (an oil droplet emulsion of monophosphoryl lipid A and mycobacterial cell wall skeleton). KLH (keyhole limpet hemocyanin) and bovine serum albumin are examples of suitable carrier proteins used in vaccine compositions. Alternatively or additionally, the peptide may be attached, covalently or otherwise, to proteins such as MHC molecules and/or antibodies (for example, see King et al. Cancer Immunol immunother. 2013 Jun; 62(6): 1093-105). Alternatively or additionally, the peptides may be encapsulated into liposomes (for example see Adamina et al. Br J Cancer. 2004 Jan 12; 90(1): 263-9). Such modified peptides may not correspond to any molecule that exists in nature.

[0069] Peptides of the invention can be synthesised easily by Merrifield synthesis, also known as solid phase synthesis, or any other peptide synthesis methodology. GMP grade peptide is produced by solid-phase synthesis techniques by Multiple Peptide Systems, San Diego, CA. As such, the peptides may be immobilized, for example to a solid support, such as a bead. Alternatively, the peptide may be recombinantly produced, if so desired, in accordance with methods known in the art. Such methods typically involve the use of a vector comprising a nucleic acid sequence encoding the peptide to be expressed, to express the polypeptide in vivo, for example, in bacteria, yeast, insect or mammalian cells. Alternatively, in vitro cell-free systems may be used. Such systems are known in the art and are commercially available, for example, from Life Technologies, Paisley, UK. The peptides may be isolated and/or may be provided in substantially pure form. For example, they may be provided in a form, which is substantially free of other peptides or proteins.

[0070] In a fourth aspect, the invention is directed to an isolated, ex vivo complex comprising:

(i) the amino acid sequence of any one of SEQ ID NOs: 1-16, or

(ii) the amino acid sequence of any one of SEQ ID NOs: 1-16, with the exception of 1 , 2, or 3 amino acid substitution(s), and/or 1 , 2, or 3 amino acid insertion(s), and/or 1 , 2, or 3 amino acid deletion(s); and

(b) an MHC II molecule. In illustrated examples of the complex of the invention, the peptide may have up to 17 amino acid residues and may comprise or consist of the amino acid sequence of any one of SEQ ID NOs: 1-16. In illustrated examples of the complex of the invention, the peptide may consist of from 13 to 16 amino acids. In another illustrated example of the complex of the invention, the peptide may consist of an amino acid sequence of any one of SEQ ID NOs: 1-16.

[0071] As is known in the art, the ability of a peptide to form an immunogenic complex with a given MHC type, and thus activate T cells, is determined by the stability and affinity of the peptide-MHC interaction (van der Burg et al., J Immunol. 1996 May 1 ; 156(9): 3308-14). The skilled person can, for example, determine whether or not a given polypeptide forms a complex with an MHC molecule by determining whether the MHC can be refolded in the presence of the polypeptide. If the polypeptide does not form a complex with MHC, then MHC will not refold. Refolding is commonly confirmed using an antibody that recognises MHC in a folded state only. Further details can be found in Garboczi et al., Proc Natl Acad Sci USA. 1992 Apr. 15; 89(8): 3429-33. Alternatively, the skilled person may determine the ability of a peptide to stabilize MHC on the surface of TAP-deficient cell lines, such as T2 cells, or other biophysical methods to determine interaction parameters (Harndahl et al., J Biomol Screen. 2009 Feb.; 14(2): 173-80).

[0072] The complex of the invention may be isolated and/or may be in a substantially pure form. For example, the complex may be provided in a form, which is substantially free of other peptides or proteins. It should be noted that in the context of the present invention, the term “MHC molecule” includes recombinant MHC molecules, non-naturally occurring MHC molecules and functionally equivalent fragments of MHC, including derivatives or variants thereof, provided that peptide binding is retained. For example, MHC molecules may be fused to a therapeutic moiety, attached to a solid support, in soluble form, attached to a tag, biotinylated and/or in multimeric form. The peptide may be covalently attached to the MHC.

[0073] Peptide-MHC complexes of the invention may be provided in soluble form, or may be immobilized by attachment to a suitable solid support. Examples of solid supports include, but are not limited to, a bead, a membrane, sepharose, a magnetic bead, a plate, a tube, a column. Peptide-MHC complexes may be attached to an ELISA plate, a magnetic bead, or a surface plasmon reasonance biosensor chip. Methods of attaching peptide-MHC complexes to a solid support are known to the skilled person, and include, for example, using an affinity binding pair, e.g. biotin and streptavidin, or antibodies and antigens. In a preferred embodiment, peptide-MHC complexes are labelled with biotin and attached to streptavidin-coated surfaces.

[0074] In a fifth aspect, the invention is directed to a nucleic acid sequence encoding the antigen recognizing construct or the T cell receptor according to the first or second aspect of the invention or a peptide according to the third aspect of the invention.

[0075] The term “nucleic acid”, as used herein, includes “polynucleotide”, “oligonucleotide” and “nucleic acid molecule”, and generally means a polymer of DNA or RNA, which can be single-stranded or double-stranded, synthesized or obtained (e.g., isolated and/or purified) from natural sources, which can contain natural, non-natural or altered nucleotides, and which can contain a natural, non-natural or altered internucleotide linkage, such as a phosphoroamidate linkage or a phosphorothioate linkage, instead of the phosphodiester found between the nucleotides of an unmodified oligonucleotide.

[0076] In the sixth aspect, the invention is directed to a vector comprising the nucleic acid sequence according to the fifth aspect of the invention. [0077] In the context of the present invention, the term "vector" encompasses a DNA molecule, such as a plasmid, bacteriophage, phagemid, virus or other vehicle, which contains one or more heterologous or recombinant nucleotide sequences (e.g., an above-described nucleic acid molecule of the invention, under the control of a functional promoter and, possibly, also an enhancer) and is capable of functioning as a vector in the sense understood by those of ordinary skill in the art. Appropriate phage and viral vectors include, but are not limited to, lambda (X) bacteriophage, EMBL bacteriophage, simian virus 40, bovine papilloma virus, Epstein-Barr virus, adenovirus, herpes virus, vaccinia virus, Moloney murine leukemia virus, Harvey murine sarcoma virus, murine mammary tumor virus, lentivirus and Rous sarcoma virus.

[0078] Desirably, the vector is an expression vector or a recombinant expression vector. The term “recombinant expression vector” refers in context of the present invention to a nucleic acid construct that allows for the expression of an mRNA, protein or polypeptide in a suitable host cell. The recombinant expression vector of the invention can be any suitable recombinant expression vector, and can be used to transform or transfect any suitable host. Suitable vectors include those designed for propagation and expansion or for expression or both, such as plasmids and viruses. Examples of animal expression vectors include pEUK-CI, pMAM and pMAMneo. In one illustrated example, the recombinant expression vector is a viral vector, e.g., a retroviral vector. The recombinant expression vector comprises regulatory sequences, such as transcription and translation initiation and termination codons, which are specific to the type of host cell (e.g., bacterium, fungus, plant, or animal) into which the vector is to be introduced and in which the expression of the nucleic acid of the invention shall be performed. Furthermore, the vector of the invention may include one or more marker genes, which allow for selection of transformed or transfected hosts. The recombinant expression vector can comprise a native or normative promoter operably linked to the nucleotide sequence encoding the constructs of the invention, or to the nucleotide sequence which is complementary to or which hybridizes to the nucleotide sequence encoding the constructs of the invention. The selection of promoters include, e.g., strong, weak, inducible, tissue-specific and developmental-specific promoters. The promoter can be a non-viral promoter or a viral promoter. The inventive recombinant expression vectors can be designed for either transient expression, for stable expression, or for both. Also, the recombinant expression vectors can be made for constitutive expression or for inducible expression.

[0079] The invention will be further explained in the following making reference to either, several or all of these aspects. If reference is only made to one of these aspects, it is understood by the person skilled in the art, that this reference nevertheless includes references to all other aspects of the invention, if applicable.

[0080] In the seventh aspect, the invention is directed to a host cell comprising the antigen recognizing construct or T cell receptor according to the first or second aspect of the invention, or the peptide according to the third aspect of the invention, or the complex of the fourth aspect of the invention, or the nucleic acid sequence according to the fifth aspect of the invention, or the vector according to the sixth aspect of the invention.

[0081] Specifically, the host cell of the invention comprises a nucleic acid, or a vector as described herein above. The host cell can be an eukaryotic cell, e.g., plant, animal, fungi, or algae, or can be a prokaryotic cell, e.g., bacteria or protozoa. The host cell can be a cultured cell or a primary cell, i.e. , isolated directly from an organism, e.g., a human. The host cell can be an adherent cell or a suspended cell, i.e., a cell that grows in suspension. For purposes of producing a recombinant TCR, polypeptide, or protein, the host cell is e.g. a mammalian cell. In another illustrated example, the host cell is a human cell. While the host cell can be of any cell type, it can originate from any type of tissue, and can be of any developmental stage, the host cell may be a peripheral blood leukocyte (PBL) or a peripheral blood mononuclear cell (PBMC). In another illustrated example, the host cell is a T cell. The T cell can be any T cell, such as a cultured T cell, e.g., a primary T cell, or a T cell from a cultured T cell line, e.g., Jurkat, SupTI, etc., or a T cell obtained from a mammal, specifically a T cell or T cell precursor from a human patient. If obtained from a mammal, the T cell can be obtained from numerous sources, including, but not limited to, blood, bone marrow, lymph node, the thymus, or other tissues or fluids. T cells can also be enriched for or purified. In another illustrated example, the T cell is a human T cell. In another illustrated example, the T cell is a T cell isolated from a human. The T cell can be any type of T cell and can be of any developmental stage, including, but not limited to, CD4positive and/or CD8positive, CD4 positive helper T cells, e.g., Th1 and Th2 cells, CD8 positive T cells (e.g., cytotoxic T cells), tumor infiltrating cells (TILs), memory T cells, naive T cells, and the like. In another illustrated example, the T cell is a CD8 positive T cell or a CD4 positive T cell.

[0082] In an illustrative example, the host cell of the invention is a lymphocyte, specifically a T lymphocyte, such as a CD4 or CD8 positive T-cell. The host cell furthermore may be specifically a tumor reactive T cell specific for KK-LC-1 expressing tumor cells.

[0083] In the eighth aspect, the invention is directed to the antigen recognizing construct or T cell receptor according to the first or second aspect of the invention, or the peptide according to the third aspect of the invention, or the complex of the fourth aspect of the invention, or the nucleic acid sequence according to the fifth aspect of the invention, or the vector according to the sixth aspect of the invention, for use in medicine. [0084] In the ninth aspect, the invention is directed to the antigen recognizing construct or T cell receptor according to the first or second aspect of the invention, or the peptide according to the third aspect of the invention, or the complex of the fourth aspect of the invention, or the nucleic acid sequence according to the fifth aspect of the invention, or the vector according to the sixth aspect of the invention, for use in the prevention and/or treatment of a disease.

[0085] With regard to the ninth aspect of the invention, the disease may be a cancer, such as a disease selected from the group consisting of cervical cancer, head and neck cancer, melanoma, lung cancer, esophageal cancer, gastric cancer, breast cancer, ovarian cancer, mesothelioma cancer, bladder cancer, anal cancer, chondrosarcoma cancer, osteosarcoma cancer, sarcoma cancer, adenoma cancer, primitive neuroectodermal cancer (primitive neuroectodermal tumor (PNET)), and combinations thereof.

[0086] The lung cancer may be, but is not limited to, squamous cell carcinoma of the lung, non-small cell lung cancer and small cell lung cancer. In other illustrative examples, the breast cancer may be, but is not limited to, ductal breast cancer, tubular breast cancer, medullary breast cancer and combinations thereof. In yet another illustrative example, the gastric cancer may be gastric adenocarcinoma cancer. Turning to sarcoma cancer, the sarcoma cancer may be, but is no limited to, chondrosarcoma cancer, osteosarcoma cancer and combinations thereof. The adenoma cancer may include, but is also not limited to, gastric adenocarcinoma, pancreatic adenocarcinoma and combinations thereof.

[0087] The terms “treat” and “prevent” as well as words stemming therefrom, like “treatment” or “prevention”, as used herein, do not necessarily imply 100% or complete treatment or prevention. Rather, there are varying degrees of treatment or prevention of which one of ordinary skill in the art recognizes as having a potential benefit or therapeutic effect. In this respect, the inventive methods can provide any amount of any level of treatment or prevention of cancer in a mammal. Furthermore, the treatment or prevention provided by the inventive method can include treatment or prevention of one or more conditions or symptoms of the cancer being treated or prevented. For example, treatment or prevention can include promoting the regression of a tumor. Also, for purposes herein, “prevention” can encompass delaying the onset of the cancer, or a symptom or condition thereof.

[0088] According to the ninth aspect of the invention, the disease may be a malignant or benign tumor disease. [0089] The term “tumor” or “tumor disease” in the context of the present invention denotes a disease selected from melanomas, hepatocellular carcinomas, intra- and extrahepatic cholangiocellular carcinomas, squamous cell carcinomas, adenocarcinomas as well as undifferentiated carcinomas of the head, neck, lung or esophagus, colorectal carcinomas, chondrosarcomas, osteosarcomas, medulloblastomas, neuroblastomas, non-squamous cell carcinomas of the head or neck, ovarian tumors, lymphomas, acute and chronic lymphocytic leukemias, acute and chronic myeloid leukemia, bladder carcinomas, prostate carcinomas, pancreatic adenocarcinomas, mammary carcinomas and gastric carcinomas. In illustrated examples, diseases to be treated by the products and/or methods of the invention include melanoma, non-small-cell lung cancer, pancreatic adenocarcinoma and cholangiocellular carcinoma.

[0090] Within the ninth aspect of the invention, the disease may be a tumor that expresses Kita-Kyushu Lung Cancer Antigen 1 (KK-LC-1). Specifically, the disease may be a solid tumor that expresses Kita-Kyushu Lung Cancer Antigen 1 (KK-LC-1). In an illustrated example, the disease may be an advanced-stage metastatic solid tumor that expresses Kita-Kyushu Lung Cancer Antigen 1 (KK-LC-1).

[0091] Dealing with the solid tumor to be treated, the methods of the inventions can be applied to any solid tumor, which has been found to express KK-LC-1 at a threshold level as described herein. This tumor can be a solid tumor that is already known to express KK-LC-1 , but also any tumor, for which it will be found that the tumor expresses KK-LC-1 at a given threshold as described herein. Accordingly, apart from solid tumors, such as the ones that are expressly mentioned here, the present invention addresses also solid tumors that have only a very small KK-LC-1 positive population, as long as the population is found to express KK-LC-1 at a threshold level as described herein.

[0092] Turning now to the solid tumor types in more detail, the patient may have, for example, been diagnosed with a genotype and/or advanced-stage metastatic solid tumor that express KK-LC-1. Examples of a solid tumor to be treated may include, but are not limited to, cervical cancer, head and neck cancer, melanoma, lung cancer, esophageal cancer, gastric cancer, breast cancer, ovarian cancer, mesothelioma cancer, bladder cancer, anal cancer, chondrosarcoma cancer, osteosarcoma cancer, sarcoma cancer, adenoma cancer, primitive neuroectodermal cancer (primitive neuroectodermal tumor (PNET)), or combinations thereof, to mention only a few.

[0093] In illustrative examples of the solid tumor types mentioned above, the lung cancer may be, but is not limited to, non-small cell lung cancer (NSCLC), including squamous cell carcinoma of the lung, adenocarcinoma of the lung, large cell carcinoma of the lung and other histologic types of NSCLC, or small cell lung cancer. In other illustrative examples, the breast cancer may be, but is not limited to, ductal breast cancer, ductal-invasive breast cancer, invasive breast cancer, tubular breast cancer, medullary breast cancer or combinations thereof. In yet other illustrative examples, the gastric cancer may be gastric adenocarcinoma or squamous cell cancer. Turning to sarcoma cancer, the sarcoma cancer may be, but is no limited to, chondrosarcoma cancer, osteosarcoma cancer or combinations thereof. The adenoma cancer may include, but is also not limited to, gastric adenocarcinoma, pancreatic adenocarcinoma or combinations thereof.

[0094] The present invention can be applied to any solid tumor that either shows a homogenous or a heterogenous KK-LC-1 expression. In this context, a tumor is herein considered homogeneously positive with respect to KK-LC-1 expression, when all cell samples taken from the same tumor have at least 5% KK-LC-1 positive cells. A solid tumor is herein considered KK-LC-1 negative, when all cell samples taken from the same tumor do not show expression of KK-LC-1. Finally, a tumor is herein considered heterogeneously positive with respect to KK-LC-1 expression when positive and negative results for KK-LC-1 expression are obtained in tumor cell samples taken from the same tumor. In illustrative terms, using tumor cell samples, a tumor is considered i) homogeneously positive, when all interpretable tissue spots have at least 5 % KK-LC-1 positive tumor cells, while it is considered ii) negative when all tissue spots have a negative immunohistochemistry result. In line with the above, a tumor is considered heterogeneously positive, when positive and negative tissue spots are found to be present in the same tumor.

[0095] The tenth aspect of the invention is directed to a use of the antigen recognizing construct or the T cell receptor according to the first or the second aspect of the invention, or the peptide according to the third aspect of the invention, or the complex of the fourth aspect of the invention, or the nucleic acid sequence according to the fifth aspect of the invention, or the vector according to the sixth aspect of the invention, or the host cell according to the seventh aspect of the invention, for the manufacture of a medicament for treating a disease. The disease may be a malignant or benign tumor disease, but is not limited thereto. In yet another illustrative example, the disease may be a solid tumor that expresses Kita-Kyushu Lung Cancer Antigen 1 (KK-LC-1). Without being limited to it, the disease is an advanced-stage metastatic solid tumor that expresses Kita-Kyushu Lung Cancer Antigen 1 (KK-LC-1).

[0096] With regard to the tenth aspect of the invention, the disease may be a cancer, such as a disease selected from the group consisting of cervical cancer, head and neck cancer, melanoma, lung cancer, esophageal cancer, gastric cancer, breast cancer, ovarian cancer, mesothelioma cancer, bladder cancer, anal cancer, chondrosarcoma cancer, osteosarcoma cancer, sarcoma cancer, adenoma cancer, primitive neuroectodermal cancer (primitive neuroectodermal tumor (PNET)), and combinations thereof. The lung cancer may be, but is not limited to, squamous cell carcinoma of the lung, non-small cell lung cancer and small cell lung cancer. In other illustrative examples, the breast cancer may be, but is not limited to, ductal breast cancer, tubular breast cancer, medullary breast cancer and combinations thereof. In yet another illustrative example, the gastric cancer may be gastric adenocarcinoma cancer. Turning to sarcoma cancer, the sarcoma cancer may be, but is no limited to, chondrosarcoma cancer, osteosarcoma cancer and combinations thereof. The adenoma cancer may include, but is also not limited to, gastric adenocarcinoma, pancreatic adenocarcinoma and combinations thereof.

[0097] The eleventh aspect of the invention is directed to a method of treating a disease, comprising the step of administering a therapeutically effective amount of the antigen recognizing construct or the T cell receptor according to the first or the second aspect of the invention, or the peptide according to the third aspect of the invention, or the complex of the fourth aspect of the invention, or the nucleic acid sequence according to the fifth aspect of the invention, or the vector according to the sixth aspect of the invention, or the host cell according to the seventh aspect of the invention. The disease may be a malignant or benign tumor disease, but is not limited thereto. In yet another illustrative example, the disease may be a tumor that expresses Kita-Kyushu Lung Cancer Antigen 1 (KK-LC-1). Without being limited to it, the disease may be an advanced-stage metastatic solid tumor that expresses Kita-Kyushu Lung Cancer Antigen 1 (KK-LC-1).

[0098] With regard to the eleventh aspect of the invention, the disease may be a cancer, such as a disease selected from the group consisting of cervical cancer, head and neck cancer, melanoma, lung cancer, esophageal cancer, gastric cancer, breast cancer, ovarian cancer, mesothelioma cancer, bladder cancer, anal cancer, chondrosarcoma cancer, osteosarcoma cancer, sarcoma cancer, adenoma cancer, primitive neuroectodermal cancer (primitive neuroectodermal tumor (PNET)), and combinations thereof. The lung cancer may be, but is not limited to, squamous cell carcinoma of the lung, non-small cell lung cancer and small cell lung cancer. In other illustrative examples, the breast cancer may be, but is not limited to, ductal breast cancer, tubular breast cancer, medullary breast cancer and combinations thereof. In yet another illustrative example, the gastric cancer may be gastric adenocarcinoma cancer. Turning to sarcoma cancer, the sarcoma cancer may be, but is no limited to, chondrosarcoma cancer, osteosarcoma cancer and combinations thereof. The adenoma cancer may include, but is also not limited to, gastric adenocarcinoma, pancreatic adenocarcinoma and combinations thereof. [0099] Addressing now in more detail the treatment of the disease, e.g. the tumor, the method of treatment can apply any suitable cancer treatment, for example, a treatment with a small molecule chemotherapeutic drug or immunotherapy. An immunotherapy treatment may comprise administering to the patient a therapeutically effective amount of an adoptive cell therapy agent or an agent specifically binding KK-LC-1.

[00100] Examples of cell therapy agents may be genetically modified cells of the immune systems such as T cells or natural killer (NK) cells. Such genetically modified cells include chimeric antigen receptor T-cells (CAR T-cells, see Jakobsen & Gjerstorff “CAR T-Cell Cancer Therapy Targeting Surface Cancer/Testis Antigens”, Front. Immunol. 2 September 2020, Article 01568, doi: 10.3389/fimmu.2020.01568) or genetically modified T-cells that express a T cell receptor that specifically binds KK-LC-1. The genetically modified cells may be autologous cells derived from the patient to be treated but also allogeneic cells, i.e., cells that are obtained not from the patient of interest, but cells that have been derived from a “universal” donor cell. This “universal” donor cell may be derived from naturally occurring cells, such as T cells or NK cells from a human donor (cf, in this respect, for example, see the review article of Perez et al., Off- the-Shelf Allogeneic T Cell Therapies for Cancer: Opportunities and Challenges Using Naturally Occurring “Universal” Donor T Cells”, Front. Immunol., 11 November 2020, Article 583716, https://doi.org/10.3389/fimmu.2020.583716). It is however also possible to derive such “universal” donor cells from induced pluripotent stem cells (iPSC), cf. the review article of Flahou et al., “Fit-For-AII iPSC-Derived Cell Therapies and Their Evaluation in Humanized Mice With NK Cell Immunity” Front. Immunol., 2 April 2021, Article 662360, https://doi.org/10.3389/fimmu.2021.662360). In case genetically modified T cells are used as cell therapy agent, the T cells may be any suitable phenotype, for example, but not limited to, CD8+ T cells, CD4+ T cells or a combination thereof. Regardless of whether autologous (patient derived) T cells or allogeneic T cells are used, the T cells may express a recombinant T cell receptor (TCR) that specifically binds KK-LC-1.

[00101] When cellular product/agents such as genetically modified T cells are used for the method of treatment of the invention, such cells can be used in any suitable dosage (therapeutically effective amount). The dosage of the T cells administered to the patient, defined as the total number of T cells, may be from about 0.5 x 10⁷ T cells to about 1 x 10¹⁰ T cells. Exemplary dosages of the T cells administered to the patient, defined as the total number of T cells, may be about 0.75 x 10⁸ T cells, about 1 x 10⁸ cells T cells, about 1 x 10⁹ T cells, about 3 x 10⁹ T cells, about 4 x 10⁹ T cells, about 5 x 10⁹ T cells, about 6 x 10⁹ T cells, about 7 x 10⁹ T cells, about 8 x 10⁹ T cells, or about 9 x 10⁹ T cells. The dosage of the T cells administered to the patient, defined as the total number of T cells, may thus be in the range of about 1 x 10⁹ cells to about 9 x 10⁹ cells or in the rage of about 3 x 10⁹ cells to about 9 x 10⁹ cells. It is noted here that as used herein with respect to the dosage/number of cells used for administration, the term "about" means to include a deviation from the respective value of up to 1%, of up to 2 %, of up to 3 %, of up to 4 %, of up to 5%, or up to and including 10% of the given value. This means, for example, a dosage of “about 1 x 10⁹ T cells” may include a total number of cells ranging from 1 x 10⁹ % ± 10 %, i.e. from 0.9 x 10⁹ to 1.1 x 10⁹ of T cells expressing a KK-LC-1 binding TCR.

[00102] In accordance with the above disclosure, the invention also provides a pharmaceutical composition as a twelfth aspect of the invention comprising the antigen recognizing construct or the T cell receptor according to the first or the second aspect of the invention, or the peptide according to the third aspect of the invention, or the complex of the fourth aspect of the invention, or the nucleic acid sequence according to the fifth aspect of the invention, or the vector according to the sixth aspect of the invention, or the host cell according to the seventh aspect of the invention.

[00103] This pharmaceutical composition may be in any suitable form, (depending upon the desired method of administering it to a patient). It may be provided in unit dosage form, will generally be provided in a sealed container and may be provided as part of a kit. Such a kit would normally (although not necessarily) include instructions for use. It may include a plurality of said unit dosage forms. Suitable compositions and methods of administration are known to those skilled in the art, for example, see Johnson et al., Blood. 2009 Jul 16; 114(3): 535-46, with reference to clinical trial numbers NCI-07-C- 0175 and NCI-07-C-0174. Cells in accordance may be supplied as part of a sterile, pharmaceutical composition, which will normally include a pharmaceutically acceptable carrier. For example, T cells transfected with TCRs of the invention may be provided in pharmaceutical composition together with a pharmaceutically acceptable carrier. The pharmaceutically acceptable carrier may be a cream, emulsion, gel, liposome, nanoparticle or ointment.

[00104] The pharmaceutical composition may be adapted for administration by any appropriate route such as a parenteral (including subcutaneous, intramuscular, or intravenous), enteral (including oral or rectal), inhalation or intranasal routes. Such compositions may be prepared by any method known in the art of pharmacy, for example, by mixing the active ingredient with the carrier(s) or excipient(s) under sterile conditions.

[00105] In illustrative examples of the pharmaceutical composition of the invention, the total number of T cells comprised in the composition may be about 0.75 x 10⁸ T cells, about 1 x 10⁸ cells, about 1 x 10⁹ T cells, about 3 x 10⁹ T cells, about 4 x 10⁹ T cells, about 5 x 10⁹ T cells, about 6 x 10⁹ T cells, about 7 x 10⁹ T cells, about 8 x 10⁹ T cells or about 9 x 1O⁹T cells.

[00106] The pharmaceutical composition may further comprise one or more pharmaceutically acceptable carrier. Any pharmaceutically acceptable carrier can be used, as long as the carrier does not impact the viability of the T cells to be administered and as long as the carrier is suitable for the chosen route of administration of the pharmaceutical composition. The pharmaceutical acceptable carrier may be a physiological saline solution, optionally with components such as human serum albumin that can improve the viability of the T cells that express the KK-LC-1 binding TCR. It is also possible that the KK-LC-1 expressing T cells are stored, after their manufacture, in frozen form, for example, at a temperature of between -20°C and -80 °C. In this case, the pharmaceutical composition may contain cryo-protectants that have been added to protect the cells from being damaged by the freezing process. Examples of cryoprotectants that may be used here for the freezing of the pharmaceutical composition containing transduced T cells include glycerol, DMSO. These cryoprotectants can be used together with crystalloid solutions such as commercially available HypoThermosol® or PlasmaLyte-A solution, which are both approved for infusion and are available in pharmaceutical grade. Other possible media that can be used as carrier in the pharmaceutical composition are media of the “CryoStor family”, commercially available animal protein-free defined cryopreservation media from Biolife Solutions such as CyroStor2 (CS2, an optimized freeze media pre-formulated with 2% DMSO), CyroStor5 (CS5, an optimized freeze media pre-formulated with 5% DMSO), or CyroStorlO (CS10, an optimized freeze media pre-formulated with 10% DMSO).

[00107] Dealing now with a kit as a thirteenth aspect of the invention, such a kit is a kit for use in medicine comprising the antigen recognizing construct or the T cell receptor according to the first or the second aspect of the invention, or the peptide according to the third aspect of the invention, or the complex of the fourth aspect of the invention, or the nucleic acid sequence according to the fifth aspect of the invention, or the vector according to the sixth aspect of the invention, or the host cell according to the seventh aspect of the invention. Without being limited to it, the kit may be a diagnostic kit for selecting a patient for treatment of a solid tumor, wherein cells of the tumor express the Kita-Kyushu Lung Cancer Antigen 1 (KK-LC-1).

[00108] In a fourteenth aspect, the invention is directed to a method of generating an antigen recognizing construct that binds a peptide selected from the group consisting of SEQ ID NOs: 1 to 16 with a determinable affinity, wherein the method comprises: (i) immunization of a subject, and (ii) isolating the antigen recognizing construct. In an illustrated example of the fourteenth aspect of the invention, step (i) comprises at least 7 immunization steps. Each immunization step may be selected from the group consisting of gene gun immunization, adenovirus immunization, and peptide immunization.

[00109] The term “gene gun immunization”, as used herein, means the bombardment of a subject with DNA-coated particles, and is e.g. an efficient method for the administration of DNA vaccines. An illustrated example thereof is that DNA covered gold particles are injected into skin cells of mice.

[00110] The term “adenovirus immunization”, as used herein, means that Adenoviral (Ad) vectors can be used for the immunization. An illustrated example thereof is that a human adenovirus, carrying the respective KK-LC-1 coding DNA sequence, is obtained and injected into mice, e.g. intraperitoneally.

[00111] The term “peptide immunization”, as used herein, means that specific peptide is/ are used for immunization. An illustrated example thereof is the injection of a peptide derived from the KK-LC-1 protein sequence into mice, e.g. subcutaneously.

[00112] Within the fourteenth aspect of the invention, the method may comprise immunization of the subject, comprising 8 immunization steps.

[00113] In this regard, the first, second, third, fifth, seventh and eighth immunization of the subject may be carried out with gene gun immunization, the fourth immunization may be carried out with adenovirus immunization and the sixth immunization may be carried out with peptide immunization.

[00114] The invention will be further illustrated by the following non-limiting Experimental Examples.

[00115] Sequences, as used herein, are depicted in below Table 1 and Table 2.

[00116] Table 1 : Sequences as used herein.

[00117] Table 2: Further sequences as used herein.

CDRs are underlined and in bold, variable regions are underlined, constant regions are in bold.

[00118] The term “variable region” may also be called “variable domain” as used herein, both terms may be used synonymously. The term “constant region” may also be called “constant domain” as used herein, both terms may be used synonymously. [00119] These sequences of SEQ ID NOs: 83 to 104 are also depicted in Figure 6 given herein.

Experimental Examples

[00120] Example 1 : Generation of T-cells with a KK-LC-1 epitope using a derivative of ABabDII mice

[00121] ABabDR4 mice are a derivative of ABabDII mice, which were generated as described in Li et al. (2010, Nature Medicine 16, 1029-1034) and first described in Chen et al. (2017, J Exp Med. 214(11): 3417-3433). Bulk CD4+ populations responding to KK- LC-1 expressing cells were isolated from immunized mice and analysed by single cell RNA sequencing using 10X Genomics Chromium kits according to manufacturer’s instructions.

[00122] ABabDR4 mice were immunized with a pool of peptides containing among others also peptide (14 mer) KLVELEHTLLSKGF of SEQ ID NO: 1 or with the full-length KL-LC-1 protein (UniProt. Accession No. Q5H943 (KKLC1_HUMAN)) or with an adenovirus using the immunization protocol as depicted in Fig. 1. In more detail, the immunization protocols included eight immunizations and only after the 8^th step, TCR with sufficient affinity could be isolated from the mice.

[00123] TCRs characterized by the CDR3 sequences according to SEQ ID NOs: 19 and 22, 25 and 28, 31 and 34, 37 and 40, 43 and 46, 49 and 52, 55 and 58, 61 and 64, 67 and 70, 73 and 76, and 79 and 82 were generated, e.g., as shown in Table 1. The invention thus provides HLA-DR4 restricted human TCRs for KK-LC-1.

[00124] Example 2: Broad peptide specificity

[00125] TCR transduced PBLs from two or three human donors were co-cultured with HLA-DRB1*04:01 , expressing cells loaded with the different peptides (at 10 x E'⁶ M) indicated. IFNy secretion into the culture supernatant upon activation of responsive T cells was measured by Sandwich-ELISA. IFNy values were normalized to IFNy values against the peptide with the highest in silico- predicted affinity. Data for one representative donor is shown. TCRs are able to recognize a broad spectrum of peptides in the region of the core epitope.

[00126] The results of the peptide specificity measurements are given herein in Figure 3.

[00127] Example 3: Efficacy measurements of TCRs

[00128] TCR transduced T cells were co-cultured with HLA-DRB1*04:01 expressing cells loaded with one of the recognized peptides (KLVELEHTLLSKGF, SEQ ID NO: 1) at descending concentrations (10 x E'⁶ M to 10 x E'¹² M). IFNy secretion into the culture supernatant upon activation of responsive T cells was measured by Sandwich-ELISA. IFNy values were normalized to the highest IFNy secretion measured and EC₅₀ values, the half-maximal effective concentration, were calculated accordingly. Resulting secretion curves as well as EC₅₀ values are shown for one out of three representative donors in Figure 4 and Table 3 following herein.

[00129] Table 3:

[00130] The results of Example 3 are given herein in Figure 4.

[00131] Example 4:

[00132] TCR transduced PBLs from three human donors were co-cultured with HLA- DRB1 *04:01 expressing cells transduced with KK-LC-1 (LCLwO3_KK-C-1) and cells expressing KK-LC-1 transduced with CIITA (to induce MHCII expression) and HLA- DRB1*04:01 (Hela_CIITA_DR4) and corresponding controls. IFNy secretion into the culture supernatant upon activation of responsive T cells was measured by Sandwich- ELISA. Data for one representative donor is shown. Only cells expressing both HLA- DRB1*04:01 as well as KK-LC-1 are recognized by the TCRs above background (untransduced cells).

[00133] Materials and Methods

[00134] Peptide immunization was carried out by subcutaneous injection of mice with a peptide mix containing of the peptides (85% purity), incomplete Freud’s adjuvant and CpG. For DNA immunization by gene gun, gold particles were covered with pVAX plasmid DNA containing the KK-LC-1 coding DNA sequence. By means of the gene gun, these DNA covered gold particles were injected into skin cells of the mice. Human adenovirus 5, carrying the KK-LC-1 coding DNA sequence, was obtained and injected into mice intraperitoneally.

Transduction of human donor T cells as well as transduction of target cells with KK-LC-1 or CIITA and HLA-DRB1*04:01 were performed using retroviral vectors. [00135] The invention will be further illustrated by the following non-limiting items:

1. An antigen recognizing construct that binds a peptide selected from the group consisting of

SEQ ID NO: 1 (KLVELEHTLLSKGF), SEQ ID NO: 2 (KLVELEHTLLSKG),

SEQ ID NO: 3 (NKLVELEHTLLSK), SEQ ID NO: 4 (LVELEHTLLSKGF),

SEQ ID NO: 5 (NKLVELEHTLLSKG), SEQ ID NO: 6 (LVELEHTLLSKGFR),

SEQ ID NO: 7 (ENKLVELEHTLLSK), SEQ ID NO: 8 (NKLVELEHTLLSKGF),

SEQ ID NO: 9 (KLVELEHTLLSKGFR), SEQ ID NO: 10 (ENKLVELEHTLLSKG),

SEQ ID NO: 11 (LVELEHTLLSKGFRG), SEQ ID NO: 12 (VENKLVELEHTLLSK),

2. The antigen recognizing construct of item 1 , wherein the antigen recognizing construct is an antibody, or fragment thereof, or a T cell receptor (TOR), or fragment thereof.

3. The antigen recognizing construct of item 1 or item 2, wherein the antigen recognizing construct specifically binds the peptide with an EC₅₀ of less than about 1 x 10'⁸ M or of less than about 2 x 10'⁸ M or of less than about 6 x 10'⁸ M.

4. The antigen recognizing construct of item 3, wherein the EC₅₀ value was determined by the procedure as carried out in Example 3.

5. The antigen recognizing construct of any one of the preceding items, wherein the antigen recognizing construct has an antigenic specificity for Kita-Kyushu Lung Cancer Antigen 1 (KK-LC-1).

6. The antigen recognizing construct of any one of the preceding items, wherein the antigen recognizing construct binds the peptide being presented by an MHC II molecule.

7. The antigen recognizing construct of item 6, wherein the MHC II molecule is a complex of the HLA-DRA molecule and an HLA-DRB1 molecule.

8. The antigen recognizing construct of item 7, wherein the HLA-DRB1 molecule is HLA- DRB1*04:01. 9. The antigen recognizing construct of any one of the preceding items, wherein the antigen recognizing construct binds the peptide with an antigenic specificity of at least 80%.

10. The antigen recognizing construct of any one of the preceding items, wherein the antigen recognizing construct is a T cell receptor (TCR).

11. The T cell receptor of item 10, wherein the T cell receptor comprises a complementary determining region 3 (CDR3) of the a chain having at least 90% sequence identity to an amino acid sequence selected from the group consisting of SEQ ID NOs: 19, 25, 31 , 37, 43, 49, 55, 61 , 67, 73, and 79, and/or wherein the T cell receptor comprises a complementary determining region 3 (CDR3) of the 0 chain having at least 90% sequence identity to an amino acid sequence selected from the group consisting of SEQ ID NOs: 22, 28, 34, 40, 46, 52, 58, 64, 70, 76, and 82.

12. The T cell receptor of item 10 or item 11, wherein the T cell receptor comprises a complementary determining region 1 (CDR1) of the a chain having at least 90% sequence identity to an amino acid sequence selected from the group consisting of SEQ ID NOs: 17, 23, 29, 35, 41, 47, 53, 59, 65, 71 , and 77, and/or wherein the T cell receptor comprises a complementary determining region 1 (CDR1) of the 0 chain having at least 90% sequence identity to an amino acid sequence selected from the group consisting of SEQ ID NOs: 20, 26, 32, 38, 44, 50, 56, 62, 68, 74, and 80.

13. The T cell receptor of any one of items 10 to 12, wherein the T cell receptor comprises a complementary determining region 2 (CDR2) of the a chain having at least 90% sequence identity to an amino acid sequence selected from the group consisting of SEQ ID NOs: 18, 24, 30, 36, 42, 48, 54, 60, 66, 71 , and 78, and/or wherein the T cell receptor comprises a complementary determining region 2 (CDR2) of the 0 chain having at least 90% sequence identity to an amino acid sequence selected from the group consisting of SEQ ID NOs: 21, 27, 33, 39, 45, 51 , 57, 63, 69, 75, and 81.

14. The T cell receptor of any one of items 10 to 13, wherein the T cell receptor comprises a complementary determining region 3 (CDR3) of the a chain having at least 95% sequence identity to an amino acid sequence selected from the group consisting of SEQ ID NOs: 19, 25, 31, 37, 43, 49, 55, 61, 67, 73, and 79, and/or wherein the T cell receptor comprises a complementary determining region 3 (CDR3) of the 0 chain having at least 95% sequence identity to an amino acid sequence selected from the group consisting of SEQ ID NOs: 22, 28, 34, 40, 46, 52, 58, 64, 70, 76, and 82.

15. The T cell receptor of any one of items 10 to 14, wherein the T cell receptor comprises a complementary determining region 1 (CDR1) of the a chain having at least 95% sequence identity to an amino acid sequence selected from the group consisting of SEQ ID NOs: 17, 23, 29, 35, 41, 47, 53, 59, 65, 71 , and 77, and/or wherein the T cell receptor comprises a complementary determining region 1 (CDR1) of the 0 chain having at least 95% sequence identity to an amino acid sequence selected from the group consisting of SEQ ID NOs: 20, 26, 32, 38, 44, 50, 56, 62, 68, 74, and 80.

16. The T cell receptor of any one of items 10 to 15, wherein the T cell receptor comprises a complementary determining region 2 (CDR2) of the a chain having at least 95% sequence identity to an amino acid sequence selected from the group consisting of SEQ ID NOs: 18, 24, 30, 36, 42, 48, 54, 60, 66, 71 , and 78, and/or wherein the T cell receptor comprises a complementary determining region 2 (CDR2) of the 0 chain having at least 95% sequence identity to an amino acid sequence selected from the group consisting of SEQ ID NOs: 21 , 27, 33, 39, 45, 51 , 57, 63, 69, 75, and 81.

17. The T cell receptor of any one of items 10 to 15, comprising:

18. and an a chain CDR3 comprising or consisting of the amino acid sequence of SEQ ID NO: 19; or

30, and an a chain CDR3 comprising or consisting of the amino acid sequence of SEQ ID NO:

31; or

36, and an a chain CDR3 comprising or consisting of the amino acid sequence of SEQ ID NO:

37; or

43; or

49; or

55; or

61; or (i) an a chain CDR1 comprising or consisting of the amino acid sequence of SEQ ID NO:

79.

18. The T cell receptor of any one of items 10 to 17, comprising:

(a) a p chain CDR1 comprising or consisting of the amino acid sequence of SEQ ID NO: 20, a p chain CDR2 comprising or consisting of the amino acid sequence of SEQ ID NO: 21, and a p chain CDR3 comprising or consisting of the amino acid sequence of SEQ ID NO: 22; or

(d) a chain CDR1 comprising or consisting of the amino acid sequence of SEQ ID NO: 38, a p chain CDR2 comprising or consisting of the amino acid sequence of SEQ ID NO: 39, and a p chain CDR3 comprising or consisting of the amino acid sequence of SEQ ID NO: 40; or

(i) a p chain CDR1 comprising or consisting of the amino acid sequence of SEQ ID NO: 68, a p chain CDR2 comprising or consisting of the amino acid sequence of SEQ ID NO: 69, and a chain CDR3 comprising or consisting of the amino acid sequence of SEQ ID NO: 70; or

19. The T cell receptor of any one of items 10 to 18, comprising:

19, a p chain CDR1 comprising or consisting of the amino acid sequence of SEQ ID NO: 20, a p chain CDR2 comprising or consisting of the amino acid sequence of SEQ ID NO: 21 , and a p chain CDR3 comprising or consisting of the amino acid sequence of SEQ ID NO: 22; or

49, a chain CDR1 comprising or consisting of the amino acid sequence of SEQ ID NO: 50, a p chain CDR2 comprising or consisting of the amino acid sequence of SEQ ID NO: 51, and a p chain CDR3 comprising or consisting of the amino acid sequence of SEQ ID NO: 52, or

67, a p chain CDR1 comprising or consisting of the amino acid sequence of SEQ ID NO: 68, a chain CDR2 comprising or consisting of the amino acid sequence of SEQ ID NO: 69, and a p chain CDR3 comprising or consisting of the amino acid sequence of SEQ ID NO: 70, or

20. A T cell receptor having antigenic specificity for KK-LC-1 , wherein the TCR comprises (a) an a chain CDR1 comprising or consisting of the amino acid sequence of SEQ ID NO: 17, an a chain CDR2 comprising or consisting of the amino acid sequence of SEQ ID NO: 18, and an a chain CDR3 comprising or consisting of the amino acid sequence of SEQ ID NO: 19; or

(f) an a chain CDR1 comprising or consisting of the amino acid sequence of SEQ ID NO: 47, an a chain CDR2 comprising or consisting of the amino acid sequence of SEQ ID NO: 48, and an a chain CDR3 comprising or consisting of the amino acid sequence of SEQ ID NO: 49; or

79.

21. A T cell receptor having antigenic specificity for KK-LC-1 , wherein the TCR comprises (a) a p chain CDR1 comprising or consisting of the amino acid sequence of SEQ ID NO: 20, a chain CDR2 comprising or consisting of the amino acid sequence of SEQ ID NO: 21, and a p chain CDR3 comprising or consisting of the amino acid sequence of SEQ ID NO: 22; or

(f) a p chain CDR1 comprising or consisting of the amino acid sequence of SEQ ID NO: 50, a p chain CDR2 comprising or consisting of the amino acid sequence of SEQ ID NO: 51 , and a p chain CDR3 comprising or consisting of the amino acid sequence of SEQ ID NO: 52; or

(g) a chain CDR1 comprising or consisting of the amino acid sequence of SEQ ID NO: 56, a p chain CDR2 comprising or consisting of the amino acid sequence of SEQ ID NO: 57, and a p chain CDR3 comprising or consisting of the amino acid sequence of SEQ ID NO: 58; or

(i) a p chain CDR1 comprising or consisting of the amino acid sequence of SEQ ID NO:

68, a p chain CDR2 comprising or consisting of the amino acid sequence of SEQ ID NO: 69, and a p chain CDR3 comprising or consisting of the amino acid sequence of SEQ ID NO: 70; or

(j) a p chain CDR1 comprising or consisting of the amino acid sequence of SEQ ID NO:

74, a p chain CDR2 comprising or consisting of the amino acid sequence of SEQ ID NO: 75, and a p chain CDR3 comprising or consisting of the amino acid sequence of SEQ ID NO: 76, or

22. A T cell receptor having antigenic specificity for KK-LC-1 , wherein the TCR comprises

19, a p chain CDR1 comprising or consisting of the amino acid sequence of SEQ ID NO: 20, a chain CDR2 comprising or consisting of the amino acid sequence of SEQ ID NO: 21, and a p chain CDR3 comprising or consisting of the amino acid sequence of SEQ ID NO: 22; or

(d) an a chain CDR1 comprising or consisting of the amino acid sequence of SEQ ID NO: 35, an a chain CDR2 comprising or consisting of the amino acid sequence of SEQ ID NO: 36, an a chain CDR3 comprising or consisting of the amino acid sequence of SEQ ID NO: 37, a p chain CDR1 comprising or consisting of the amino acid sequence of SEQ ID NO: 38, a chain CDR2 comprising or consisting of the amino acid sequence of SEQ ID NO: 39, and a p chain CDR3 comprising or consisting of the amino acid sequence of SEQ ID NO: 40; or

49, a p chain CDR1 comprising or consisting of the amino acid sequence of SEQ ID NO: 50, a p chain CDR2 comprising or consisting of the amino acid sequence of SEQ ID NO: 51, and a p chain CDR3 comprising or consisting of the amino acid sequence of SEQ ID NO: 52, or

55, a p chain CDR1 comprising or consisting of the amino acid sequence of SEQ ID NO: 56, a chain CDR2 comprising or consisting of the amino acid sequence of SEQ ID NO: 57, and a p chain CDR3 comprising or consisting of the amino acid sequence of SEQ ID NO: 58, or

73, a p chain CDR1 comprising or consisting of the amino acid sequence of SEQ ID NO: 74, a p chain CDR2 comprising or consisting of the amino acid sequence of SEQ ID NO: 75, and a chain CDR3 comprising or consisting of the amino acid sequence of SEQ ID NO: 76, or

23. An isolated peptide having up to 18 amino acid residues and comprising or consisting of

(i) the amino acid sequence of any one of SEQ ID NOs: 1-16, or

(ii) the amino acid sequence of any one of SEQ ID NOs: 1-16, with the exception of 1 , 2 or 3 amino acid substitution(s), and/or 1, 2 or 3 amino acid insertion(s), and/or 1 , 2 or 3 amino acid deletion(s), wherein the peptide is able to form a complex with a Major Histocompatibility Complex (MHC) II molecule.

24. The isolated peptide of item 23, wherein the peptide consists of from 13 to 16 amino acids.

25. The isolated peptide of item 23 or item 24, wherein the peptide consists of an amino acid sequence of any one of SEQ ID NOs: 1-16.

26. An isolated, ex vivo complex comprising:

(i) the amino acid sequence of any one of SEQ ID NOs: 1-16, or

(ii) the amino acid sequence of any one of SEQ ID NOs: 1-16, with the exception of 1, 2, or 3 amino acid substitution(s), and/or 1 , 2, or 3 amino acid insertion(s), and/or 1 , 2, or 3 amino acid deletion(s); and (b) an MHC II molecule.

27. The isolated, ex vivo complex of item 26, wherein the peptide consists of from 13 to 16 amino acids.

28. The isolated, ex vivo complex of item 26 or item 27, wherein the peptide consists of an amino acid sequence of any one of SEQ ID NOs: 1-16.

29. A nucleic acid sequence encoding an antigen recognizing construct or T cell receptor as defined in any one of items 1 to 22 or a peptide as defined in any one of items 23 to 25.

30. A vector comprising a nucleic acid sequence as defined in item 29.

31. A host cell comprising the antigen recognizing construct or T cell receptor according to any one of items 1 to 22, or the peptide according to any one of items 23 to 25, or the complex according to any one of items 26 to 28, or the nucleic acid sequence according to item 29, or the vector according to item 30.

32. The antigen recognizing construct or the T cell receptor according to any one of items 1 to 22, or the peptide according to any one of items 23 to 25, or the complex according to any one of items 26 to 28, or the nucleic acid sequence according to item 29, or the vector according to item 30, or the host cell according to item 31 , for use in medicine.

33. The antigen recognizing construct or the T cell receptor according to any one of items 1 to 22, or the peptide according to any one of items 23 to 25, or the complex according to any one of items 26 to 28, or the nucleic acid sequence according to item 29, or the vector according to item 30, or the host cell according to item 31 , for use in the prevention and/or treatment of a disease.

34. The antigen recognizing construct, or the T cell receptor, or the peptide, or the complex, or the nucleic acid sequence, or the vector, or the host cell according to item 33, wherein the disease is a malignant or benign tumor disease.

35. The antigen recognizing construct, or the T cell receptor, or the peptide, or the complex, or the nucleic acid sequence, or the vector, or the host cell according to item 33 or item 34, wherein the disease is a solid tumor that expresses Kita-Kyushu Lung Cancer Antigen 1 (KK-LC-1).

36. The antigen recognizing construct, or the T cell receptor, or the peptide, or the complex, or the nucleic acid sequence, or the vector, or the host cell according to item 35, wherein the disease is an advanced-stage metastatic solid tumor that expresses Kita-Kyushu Lung Cancer Antigen 1 (KK-LC-1).

37. The antigen recognizing construct, or the T cell receptor, or the peptide, or the complex, or the nucleic acid sequence, or the vector, or the host cell according to any one of items 23 to 36, wherein the disease is selected from the group consisting of cervical cancer, head cancer, neck cancer, melanoma, lung cancer, esophageal cancer, gastric cancer, breast cancer, ovarian cancer, mesothelioma cancer, bladder cancer, anal cancer, chondrosarcoma cancer, osteosarcoma cancer, sarcoma cancer, adenoma cancer, primitive neuroectodermal cancer (primitive neuroectodermal tumor (PNET)), and combinations thereof.

38. The antigen recognizing construct, or the T cell receptor, or the peptide, or the complex, or the nucleic acid sequence, or the vector, or the host cell according to item 37, wherein the lung cancer is selected from the group consisting of squamous cell carcinoma of the lung, non-small cell lung cancer and small cell lung cancer.

39. The antigen recognizing construct, or the T cell receptor, or the peptide, or the complex, or the nucleic acid sequence, or the vector, or the host cell according to item 37, wherein the breast cancer is selected from the group consisting of ductal breast cancer, tubular breast cancer, medullary breast cancer and combinations thereof.

40. The antigen recognizing construct, or the T cell receptor, or the peptide, or the complex, or the nucleic acid sequence, or the vector, or the host cell according to item 37, wherein the gastric cancer is gastric adenocarcinoma cancer.

41. The antigen recognizing construct, or the T cell receptor, or the peptide, or the complex, or the nucleic acid sequence, or the vector, or the host cell according to item 37, wherein the sarcoma cancer is selected from the group consisting of chondrosarcoma cancer, osteosarcoma cancer and combinations thereof. 42. The antigen recognizing construct, or the T cell receptor, or the peptide, or the complex, or the nucleic acid sequence, or the vector, or the host cell according to item 37, wherein the adenoma cancer is selected from the group consisting of gastric adenocarcinoma, pancreatic adenocarcinoma and combinations thereof.

43. Use of the antigen recognizing construct or the T cell receptor according to any one of items 1 to 22, or the peptide according to any one of items 23 to 25, or the complex according to any one of items 26 to 28, or the nucleic acid sequence according to item 29, or the vector according to item 30, or the host cell according to item 31, for the manufacture of a medicament for treating a disease.

44. The use of the antigen recognizing construct or the T cell receptor, or the peptide, or the complex, or the nucleic acid sequence, or the vector, or the host cell, according to item 43, wherein the disease is a malignant or benign tumor disease.

45. The use of the antigen recognizing construct or the T cell receptor, or the peptide, or the complex, or the nucleic acid sequence, or the vector, or the host cell, according to item 43 or item 44, wherein the disease is a solid tumor that expresses Kita-Kyushu Lung Cancer Antigen 1 (KK-LC-1).

46. The use of the antigen recognizing construct or the T cell receptor, or the peptide, or the complex, or the nucleic acid sequence, or the vector, or the host cell, according to item 45, wherein the disease is an advanced-stage metastatic solid tumor that expresses Kita-Kyushu Lung Cancer Antigen 1 (KK-LC-1).

47. The use of the antigen recognizing construct or the T cell receptor, or the peptide, or the complex, or the nucleic acid sequence, or the vector, or the host cell, according to any one of items 43 to 46, wherein the disease is selected from the group consisting of cervical cancer, head and neck cancer, melanoma, lung cancer, esophageal cancer, gastric cancer, breast cancer, ovarian cancer, mesothelioma cancer, bladder cancer, anal cancer, chondrosarcoma cancer, osteosarcoma cancer, sarcoma cancer, adenoma cancer, primitive neuroectodermal cancer (primitive neuroectodermal tumor (PNET)), and combinations thereof.

48. The use of the antigen recognizing construct or the T cell receptor, or the peptide, or the complex, or the nucleic acid sequence, or the vector, or the host cell, according to item 47, wherein the lung cancer is selected from the group consisting of squamous cell carcinoma of the lung, non-small cell lung cancer and small cell lung cancer.

49. The use of the antigen recognizing construct or the T cell receptor, or the peptide, or the complex, or the nucleic acid sequence, or the vector, or the host cell, according to item 47, wherein the breast cancer is selected from the group consisting of ductal breast cancer, tubular breast cancer, medullary breast cancer and combinations thereof.

50. The use of the antigen recognizing construct or the T cell receptor, or the peptide, or the complex, or the nucleic acid sequence, or the vector, or the host cell, according to item 47, wherein the gastric cancer is gastric adenocarcinoma cancer.

51. The use of the antigen recognizing construct or the T cell receptor, or the peptide, or the complex, or the nucleic acid sequence, or the vector, or the host cell, according to item 47, wherein the sarcoma cancer is selected from the group consisting of chondrosarcoma cancer, osteosarcoma cancer and combinations thereof.

52. The use of the antigen recognizing construct or the T cell receptor, or the peptide, or the complex, or the nucleic acid sequence, or the vector, or the host cell according to item 47, wherein the adenoma cancer is selected from the group consisting of gastric adenocarcinoma, pancreatic adenocarcinoma and combinations thereof.

53. A method of treating a disease, comprising the step of administering a composition comprising the antigen recognizing construct or the T cell receptor according to any one of items 1 to 22, or the peptide according to any one of items 23 to 25, or the complex according to any one of items 26 to 28, or the nucleic acid sequence according to item 29, or the vector according to item 30, or the host cell according to item 31.

54. The method of treating a disease according to item 53, wherein the disease is a malignant or benign tumor disease.

55. The method of treating a disease according to item 53 or item 54, wherein the disease is a solid tumor that expresses Kita-Kyushu Lung Cancer Antigen 1 (KK-LC-1).

56. The method of treating a disease according to item 55, wherein the disease is an advanced-stage metastatic solid tumor that expresses Kita-Kyushu Lung Cancer Antigen 1 (KK-LC-1). 57. The method of treating a disease according to any one of items 53 to 56, wherein the disease is selected from the group consisting of cervical cancer, head and neck cancer, melanoma, lung cancer, esophageal cancer, gastric cancer, breast cancer, ovarian cancer, mesothelioma cancer, bladder cancer, anal cancer, chondrosarcoma cancer, osteosarcoma cancer, sarcoma cancer, adenoma cancer, primitive neuroectodermal cancer (primitive neuroectodermal tumor (PNET)), and combinations thereof.

58. The method of treating a disease according to item 57, wherein the lung cancer is selected from the group consisting of squamous cell carcinoma of the lung, non-small cell lung cancer and small cell lung cancer.

59. The method of treating a disease according to item 57, wherein the breast cancer is selected from the group consisting of ductal breast cancer, tubular breast cancer, medullary breast cancer and combinations thereof.

60. The method of treating a disease according to item 57, wherein the gastric cancer is gastric adenocarcinoma cancer.

61. The method of treating a disease according to item 57, wherein the sarcoma cancer is selected from the group consisting of chondrosarcoma cancer, osteosarcoma cancer and combinations thereof.

62. The method of treating a disease according to item 57, wherein the adenoma cancer is selected from the group consisting of gastric adenocarcinoma, pancreatic adenocarcinoma and combinations thereof.

63. A pharmaceutical composition comprising the antigen recognizing construct or the T cell receptor according to any one of items 1 to 22, or the peptide according to any one of items 23 to 25, or the complex according to any one of items 26 to 28, or the nucleic acid sequence according to item 29, or the vector according to item 30, or the host cell according to item 31.

64. A kit for use in medicine comprising the antigen recognizing construct or the T cell receptor according to any one of items 1 to 22, or the peptide according to any one of items 23 to 25, or the complex according to any one of items 26 to 28, or the nucleic acid sequence according to item 29, or the vector according to item 30, or the host cell according to item 31.

65. The kit according to item 64, wherein the kit is a diagnostic kit for selecting a patient for treatment of a solid tumor, wherein cells of the tumor express the Kita-Kyushu Lung Cancer Antigen 1 (KK-LC-1).

66. A method of generating an antigen recognizing construct that binds a peptide selected from the group consisting of SEQ ID NOs: 1 to 16 with a determinable affinity, wherein the method comprises:

(i) immunization of a subject, and

(ii) isolating the antigen recognizing construct.

67. The method of generating an antigen recognizing construct according to item 66, wherein step (i) comprising at least 7 immunization steps.

68. The method of generating an antigen recognizing construct according to item 67, wherein each immunization step is selected from the group consisting of gene gun immunization, adenovirus immunization, and peptide immunization.

69. The method of generating an antigen recognizing construct according to any one of items 66 to 68, wherein the antigen recognizing construct is a T cell receptor.

70. The method of generating an antigen recognizing construct according to any one of items 66 to 69, wherein the method comprises immunization of the subject comprising 8 immunization steps.

71. The method of generating an antigen recognizing construct according to item 70, wherein the first, second, third, fifth, seventh and eighth immunization of the subject are carried out with gene gun immunization, the fourth immunization is carried out with adenovirus immunization and the sixth immunization is carried out with peptide immunization.

[00136] It will be readily apparent to a person skilled in the art that varying substitutions and modifications may be made to the invention disclosed herein without departing from the scope and spirit of the invention. [00137] All patents and publications mentioned in the specification are indicative of the levels of those of ordinary skill in the art to which the invention pertains. All patents and publications are herein incorporated by reference to the same extent as if each individual publication was specifically and individually indicated to be incorporated by reference.

[00138] As used herein, the term "about" means ± 20% of the indicated range, value, or structure, unless otherwise indicated. It should be understood that the terms "a" and "an", as used herein, refer to "one or more" of the enumerated components. The use of the alternative (e.g., "or") should be understood to mean either one, both, or any combination thereof of the alternatives. As used herein, the terms "include", "have", and "comprise" are used synonymously, which terms and variants thereof are intended to be construed as non-limiting.

[00139] The inventions illustratively described herein may suitably be practiced in the absence of any element or elements, limitation or limitations, not specifically disclosed herein. Thus, for example, the terms "comprising", "including", "containing", etc. shall be read expansively and without limitation. Additionally, the terms and expressions employed herein have been used as terms of description and not of limitation, and there is no intention in the use of such terms and expressions of excluding any equivalents of the features shown and described or portions thereof, but it is recognized that various modifications are possible within the scope of the invention claimed. Thus, it should be understood that although the present invention has been specifically disclosed by preferred embodiments and optional features, modification and variation of the inventions embodied therein and herein disclosed may be resorted to by those skilled in the art, and that such modifications and variations are considered to be within the scope of this invention. The invention has been described broadly and generically herein. Each of the narrower species and subgeneric groupings falling within the generic disclosure also form part of the invention. This includes the generic description of the invention with a proviso or negative limitation removing any subject matter from the genus, regardless of whether or not the excised material is specifically recited herein. In addition, where features or aspects of the invention are described in terms of Markush groups, those skilled in the art will recognize that the invention is also thereby described in terms of any individual member or subgroup of members of the Markush group. Further embodiments of the invention will become apparent from the following claims.

Claims

Claims: What is claimed is:

SEQ ID NO: 1 (KLVELEHTLLSKGF), SEQ ID NO: 2 (KLVELEHTLLSKG),

SEQ ID NO: 3 (NKLVELEHTLLSK), SEQ ID NO: 4 (LVELEHTLLSKGF),

SEQ ID NO: 5 (NKLVELEHTLLSKG), SEQ ID NO: 6 (LVELEHTLLSKGFR),

SEQ ID NO: 7 (ENKLVELEHTLLSK), SEQ ID NO: 8 (NKLVELEHTLLSKGF),

SEQ ID NO: 9 (KLVELEHTLLSKGFR), SEQ ID NO: 10 (ENKLVELEHTLLSKG),

SEQ ID NO: 11 (LVELEHTLLSKGFRG), SEQ ID NO: 12 (VENKLVELEHTLLSK),

2. The antigen recognizing construct of claim 1, wherein the antigen recognizing construct is an antibody, or fragment thereof, or a T cell receptor (TOR), or fragment thereof.

3. The antigen recognizing construct of claim 1 or claim 2, wherein the antigen recognizing construct specifically binds the peptide with an EC₅₀ of less than about 1 x 10'⁸ M or of less than about 2 x 10'⁸ M or of less than about 6 x 10'⁸ M.

4. The antigen recognizing construct of claim 3, wherein the EC₅₀ value was determined by the procedure as carried out in Example 3.

5. The antigen recognizing construct of any one of the preceding claims, wherein the antigen recognizing construct has an antigenic specificity for Kita-Kyushu Lung Cancer Antigen 1 (KK-LC-1).

6. The antigen recognizing construct of any one of the preceding claims, wherein the antigen recognizing construct binds the peptide being presented by an MHC II molecule.

7. The antigen recognizing construct of claim 6, wherein the MHC II molecule is a complex of the HLA-DRA molecule and an HLA-DRB1 molecule.

93

8. The antigen recognizing construct of claim 7, wherein the HLA-DRB1 molecule is HLA-DRB1*04:01.

9. The antigen recognizing construct of any one of the preceding claims, wherein the antigen recognizing construct binds the peptide with an antigenic specificity of at least 80%.

10. The antigen recognizing construct of any one of the preceding claims, wherein the antigen recognizing construct is a T cell receptor (TCR).

11. The T cell receptor of claim 10, wherein the T cell receptor comprises a complementary determining region 3 (CDR3) of the a chain having at least 90% sequence identity to an amino acid sequence selected from the group consisting of SEQ ID NOs: 19, 25, 31 , 37, 43, 49, 55, 61 , 67, 73, and 79, and/or wherein the T cell receptor comprises a complementary determining region 3 (CDR3) of the 0 chain having at least 90% sequence identity to an amino acid sequence selected from the group consisting of SEQ ID NOs: 22, 28, 34, 40, 46, 52, 58, 64, 70, 76, and 82.

12. The T cell receptor of claim 10 or 11, wherein the T cell receptor comprises a complementary determining region 1 (CDR1) of the a chain having at least 90% sequence identity to an amino acid sequence selected from the group consisting of SEQ ID NOs: 17, 23, 29, 35, 41, 47, 53, 59, 65, 71 , and 77, and/or wherein the T cell receptor comprises a complementary determining region 1 (CDR1) of the 0 chain having at least 90% sequence identity to an amino acid sequence selected from the group consisting of SEQ ID NOs: 20, 26, 32, 38, 44, 50, 56, 62, 68, 74, and 80.

13. The T cell receptor of any one of claims 10 to 12, wherein the T cell receptor comprises a complementary determining region 2 (CDR2) of the a chain having at least 90% sequence identity to an amino acid sequence selected from the group consisting of SEQ ID NOs: 18, 24, 30, 36, 42, 48, 54, 60, 66, 71 , and 78, and/or wherein the T cell receptor comprises a complementary determining region 2 (CDR2) of the 0 chain having at least 90% sequence identity to an amino acid sequence selected from the group consisting of SEQ ID NOs: 21, 27, 33, 39, 45, 51 , 57, 63, 69, 75, and 81.

14. The T cell receptor of any one of claims 10 to 13, wherein the T cell receptor comprises a complementary determining region 3 (CDR3) of the a chain having at least

94 95% sequence identity to an amino acid sequence selected from the group consisting of SEQ ID NOs: 19, 25, 31, 37, 43, 49, 55, 61, 67, 73, and 79, and/or wherein the T cell receptor comprises a complementary determining region 3 (CDR3) of the 0 chain having at least 95% sequence identity to an amino acid sequence selected from the group consisting of SEQ ID NOs: 22, 28, 34, 40, 46, 52, 58, 64, 70, 76, and 82.

15. The T cell receptor of any one of claims 10 to 14, wherein the T cell receptor comprises a complementary determining region 1 (CDR1) of the a chain having at least 95% sequence identity to an amino acid sequence selected from the group consisting of SEQ ID NOs: 17, 23, 29, 35, 41, 47, 53, 59, 65, 71 , and 77, and/or wherein the T cell receptor comprises a complementary determining region 1 (CDR1) of the 0 chain having at least 95% sequence identity to an amino acid sequence selected from the group consisting of SEQ ID NOs: 20, 26, 32, 38, 44, 50, 56, 62, 68, 74, and 80.

16. The T cell receptor of any one of claims 10 to 15, wherein the T cell receptor comprises a complementary determining region 2 (CDR2) of the a chain having at least 95% sequence identity to an amino acid sequence selected from the group consisting of SEQ ID NOs: 18, 24, 30, 36, 42, 48, 54, 60, 66, 71 , and 78, and/or wherein the T cell receptor comprises a complementary determining region 2 (CDR2) of the 0 chain having at least 95% sequence identity to an amino acid sequence selected from the group consisting of SEQ ID NOs: 21, 27, 33, 39, 45, 51 , 57, 63, 69, 75, and 81.

17. The T cell receptor of any one of claims 10 to 15, comprising:

95 (c) an a chain CDR1 comprising or consisting of the amino acid sequence of SEQ ID NO: 29, an a chain CDR2 comprising or consisting of the amino acid sequence of SEQ ID NO: 30, and an a chain CDR3 comprising or consisting of the amino acid sequence of SEQ ID NO: 31; or

(h) an a chain CDR1 comprising or consisting of the amino acid sequence of SEQ ID NO: 59, an a chain CDR2 comprising or consisting of the amino acid sequence of SEQ ID NO: 60, and

96 an a chain CDR3 comprising or consisting of the amino acid sequence of SEQ ID NO: 61; or

79.

18. The T cell receptor of any one of claims 10 to 17, comprising:

(a) a p chain CDR1 comprising or consisting of the amino acid sequence of SEQ ID NO: 20, a p chain CDR2 comprising or consisting of the amino acid sequence of SEQ ID NO: 21 , and a p chain CDR3 comprising or consisting of the amino acid sequence of SEQ ID NO: 22; or

(c) a p chain CDR1 comprising or consisting of the amino acid sequence of SEQ ID NO: 32,

97 a p chain CDR2 comprising or consisting of the amino acid sequence of SEQ ID NO: 33, and a chain CDR3 comprising or consisting of the amino acid sequence of SEQ ID NO: 34; or

98 (i) a p chain CDR1 comprising or consisting of the amino acid sequence of SEQ ID NO: 68, a chain CDR2 comprising or consisting of the amino acid sequence of SEQ ID NO: 69, and a p chain CDR3 comprising or consisting of the amino acid sequence of SEQ ID NO: 70; or

19. The T cell receptor of any one of claims 10 to 18, comprising:

(b) an a chain CDR1 comprising or consisting of the amino acid sequence of SEQ ID NO: 23, an a chain CDR2 comprising or consisting of the amino acid sequence of SEQ ID NO: 24,

99 an a chain CDR3 comprising or consisting of the amino acid sequence of SEQ ID NO: 25, a p chain CDR1 comprising or consisting of the amino acid sequence of SEQ ID NO: 26, a chain CDR2 comprising or consisting of the amino acid sequence of SEQ ID NO: 27, and a p chain CDR3 comprising or consisting of the amino acid sequence of SEQ ID NO: 28; or

31 , a p chain CDR1 comprising or consisting of the amino acid sequence of SEQ ID NO: 32, a p chain CDR2 comprising or consisting of the amino acid sequence of SEQ ID NO: 33, and a p chain CDR3 comprising or consisting of the amino acid sequence of SEQ ID NO: 34; or

43,

100 a p chain CDR1 comprising or consisting of the amino acid sequence of SEQ ID NO: 44, a chain CDR2 comprising or consisting of the amino acid sequence of SEQ ID NO: 45, and a p chain CDR3 comprising or consisting of the amino acid sequence of SEQ ID NO: 46; or

61 , a p chain CDR1 comprising or consisting of the amino acid sequence of SEQ ID NO: 62,

101 a p chain CDR2 comprising or consisting of the amino acid sequence of SEQ ID NO: 63, and a chain CDR3 comprising or consisting of the amino acid sequence of SEQ ID NO: 64, or

20. The T cell receptor of any one of claims 10 to 19, comprising:

(a) an a chain comprising CDR sequences comprising amino acid sequences of SEQ ID NOs: 17, 18, and 19, and a chain comprising CDR sequences comprising amino acid sequences of SEQ ID NOs: 20, 21 , and 22; or

(e) an a chain comprising CDR sequences comprising amino acid sequences of SEQ ID NO: 41 , 42, and 43, and a p chain comprising CDR sequences comprising amino acid sequences of SEQ ID NOs: 44, 45, and 46; or

(j) an a chain comprising CDR sequences comprising amino acid sequences of SEQ ID NOs: 71, 72, and 73, and a p chain comprising CDR sequences comprising amino acid sequences of SEQ ID NOs: 74, 75, and 76; or (k) an a chain comprising CDR sequences comprising amino acid sequences of SEQ ID NOs: 77, 78, and 79, and a p chain comprising CDR sequences comprising amino acid sequences of SEQ ID NOs: 80, 81, and 82.

21. The T cell receptor of any one of claims 10 to 20, wherein said TCR is in the form of an a heterodimer.

22. The T cell receptor of any one of claims 10 to 21 , wherein said TCR is in a single chain format comprising said a chain and said p chain.

23. The T cell receptor of any one of claims 10 to 22, wherein the T cell receptor comprises

(a) an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95% or at least 99% sequence identity to the variable domain of SEQ ID NO: 83, and/or an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95% or at least 99% sequence identity to the variable domain of SEQ ID NO: 84; or

(b) an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95% or at least 99% sequence identity to the variable domain of SEQ ID NO: 85, and/or an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95% or at least 99% sequence identity to the variable domain of SEQ ID NO: 86; or

(c) an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95% or at least 99% sequence identity to the variable domain of SEQ ID NO: 87, and/or an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95% or at least 99% sequence identity to the variable domain of SEQ ID NO: 88; or

(d) an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95% or at least 99% sequence identity to the variable domain of SEQ ID NO: 89, and/or an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95% or at least 99% sequence identity to the variable domain of SEQ ID NO: 90; or

(e) an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95% or at least 99% sequence identity to the variable domain of SEQ ID NO: 91 , and/or an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95% or at least 99% sequence identity to the variable domain of SEQ ID NO: 92; or

(f) an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95% or at least 99% sequence identity to the variable domain of SEQ ID NO: 93, and/or an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95% or at least 99% sequence identity to the variable domain of SEQ ID NO: 94; or

104 (g) an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95% or at least 99% sequence identity to the variable domain of SEQ ID NO: 95, and/or an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95% or at least 99% sequence identity to the variable domain of SEQ ID NO: 96; or

(h) an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95% or at least 99% sequence identity to the variable domain of SEQ ID NO: 97, and/or an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95% or at least 99% sequence identity to the variable domain of SEQ ID NO: 98; or

(i) an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95% or at least 99% sequence identity to the variable domain of SEQ ID NO: 99, and/or an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95% or at least 99% sequence identity to the variable domain of SEQ ID NO: 100; or

(j) an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95% or at least 99% sequence identity to the variable domain of SEQ ID NO: 101 , and/or an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95% or at least 99% sequence identity to the variable domain of SEQ ID NO: 102; or

(k) an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95% or at least 99% sequence identity to the variable domain of SEQ ID NO: 103, and/or an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95% or at least 99% sequence identity to the variable domain of SEQ ID NO: 104.

24. The T cell receptor of any one of claims 10 to 23, wherein the T cell receptor comprises

(a) an a chain comprising a sequence having at least 80%, at least 85%, at least 90%, at least 95% or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 83, and/or a p chain comprising a sequence having at least 80%, at least 85%, at least 90%, at least 95% or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 84; or

(b) an a chain comprising a sequence having at least 80%, at least 85%, at least 90%, at least 95% or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 85, and/or a p chain comprising a sequence having at least 80%, at least 85%, at least 90%, at least 95% or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 86; or

(c) an a chain comprising a sequence having at least 80%, at least 85%, at least 90%, at least 95% or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 87, and/or a p chain comprising a sequence having at least 80%, at least 85%, at

105 least 90%, at least 95% or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 88; or

(d) an a chain comprising a sequence having at least 80%, at least 85%, at least 90%, at least 95% or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 89, and/or a p chain comprising a sequence having at least 80%, at least 85%, at least 90%, at least 95% or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 90; or

(e) an a chain comprising a sequence having at least 80%, at least 85%, at least 90%, at least 95% or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 91 , and/or a p chain comprising a sequence having at least 80%, at least 85%, at least 90%, at least 95% or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 92; or

(f) an a chain comprising a sequence having at least 80%, at least 85%, at least 90%, at least 95% or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 93, and/or a p chain comprising a sequence having at least 80%, at least 85%, at least 90%, at least 95% or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 94; or

(g) an a chain comprising a sequence having at least 80%, at least 85%, at least 90%, at least 95% or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 95, and/or a p chain comprising a sequence having at least 80%, at least 85%, at least 90%, at least 95% or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 96; or

(h) an a chain comprising a sequence having at least 80%, at least 85%, at least 90%, at least 95% or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 97, and/or a p chain comprising a sequence having at least 80%, at least 85%, at least 90%, at least 95% or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 98; or

(i) an a chain comprising a sequence having at least 80%, at least 85%, at least 90%, at least 95% or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 99, and/or a p chain comprising a sequence having at least 80%, at least 85%, at least 90%, at least 95% or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 100; or

(j) an a chain comprising a sequence having at least 80%, at least 85%, at least 90%, at least 95% or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 101 , and/or a p chain comprising a sequence having at least 80%, at least 85%, at

106 least 90%, at least 95% or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 102; or

(k) an a chain comprising a sequence having at least 80%, at least 85%, at least 90%, at least 95% or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 103, and/or a p chain comprising a sequence having at least 80%, at least 85%, at least 90%, at least 95% or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 104.

25. A T cell receptor having antigenic specificity for KK-LC-1 , wherein the TCR comprises

(e) an a chain CDR1 comprising or consisting of the amino acid sequence of SEQ ID NO: 41 ,

107 an a chain CDR2 comprising or consisting of the amino acid sequence of SEQ ID NO:

43; or

49; or

55; or

61; or

67; or

73; or

108 (k) an a chain CDR1 comprising or consisting of the amino acid sequence of SEQ ID NO: 77, an a chain CDR2 comprising or consisting of the amino acid sequence of SEQ ID NO:

79.

26. A T cell receptor having antigenic specificity for KK-LC-1 , wherein the TCR comprises

(e) a p chain CDR1 comprising or consisting of the amino acid sequence of SEQ ID NO: 44,

109 a p chain CDR2 comprising or consisting of the amino acid sequence of SEQ ID NO: 45, and a chain CDR3 comprising or consisting of the amino acid sequence of SEQ ID NO: 46; or

110 (k) a p chain CDR1 comprising or consisting of the amino acid sequence of SEQ ID NO: 80, a chain CDR2 comprising or consisting of the amino acid sequence of SEQ ID NO: 81 , and a p chain CDR3 comprising or consisting of the amino acid sequence of SEQ ID NO: 82.

27. A T cell receptor having antigenic specificity for KK-LC-1 , wherein the TCR comprises

(c) an a chain CDR1 comprising or consisting of the amino acid sequence of SEQ ID NO: 29, an a chain CDR2 comprising or consisting of the amino acid sequence of SEQ ID NO: 30,

111 an a chain CDR3 comprising or consisting of the amino acid sequence of SEQ ID NO: 31, a p chain CDR1 comprising or consisting of the amino acid sequence of SEQ ID NO: 32, a chain CDR2 comprising or consisting of the amino acid sequence of SEQ ID NO: 33, and a p chain CDR3 comprising or consisting of the amino acid sequence of SEQ ID NO: 34; or

49,

112 a p chain CDR1 comprising or consisting of the amino acid sequence of SEQ ID NO: 50, a chain CDR2 comprising or consisting of the amino acid sequence of SEQ ID NO: 51 , and a p chain CDR3 comprising or consisting of the amino acid sequence of SEQ ID NO: 52, or

67, a p chain CDR1 comprising or consisting of the amino acid sequence of SEQ ID NO: 68,

113 a p chain CDR2 comprising or consisting of the amino acid sequence of SEQ ID NO: 69, and a chain CDR3 comprising or consisting of the amino acid sequence of SEQ ID NO: 70, or

28. A T cell receptor having antigenic specificity for KK-LC-1 , wherein the TCR comprises

114 (c) an a chain comprising CDR sequences comprising amino acid sequences of SEQ ID NOs: 29, 30, and 31, and a p chain comprising CDR sequences comprising amino acid sequences of SEQ ID NOs: 32, 33, and 34; or

(d) an a chain comprising CDR sequences comprising amino acid sequences of SEQ ID NO: 35, 36, and 37, and a chain comprising CDR sequences comprising amino acid sequences of SEQ ID NO: 38, 39, and 40; or

(f) an a chain comprising CDR sequences comprising amino acid sequences of SEQ ID NOs: 47, 48, and 49, and a p chain comprising CDR sequences comprising amino acid sequences of SEQ ID NOs: 50, 51 , and 52; or

(j) an a chain comprising CDR sequences comprising amino acid sequences of SEQ ID NOs: 23, 24, and 25, and a p chain comprising CDR sequences comprising amino acid sequences of SEQ ID NOs: 26, 27, and 28; or

29. A T cell receptor having antigenic specificity for KK-LC-1 , wherein the TCR comprises

115 (b) an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95% or at least 99% sequence identity to the variable domain of SEQ ID NO: 85, and/or an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95% or at least 99% sequence identity to the variable domain of SEQ ID NO: 86; or

(g) an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95% or at least 99% sequence identity to the variable domain of SEQ ID NO: 95, and/or an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95% or at least 99% sequence identity to the variable domain of SEQ ID NO: 96; or

116 (k) an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95% or at least 99% sequence identity to the variable domain of SEQ ID NO: 103, and/or an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95% or at least 99% sequence identity to the variable domain of SEQ ID NO: 104.

30. A T cell receptor having antigenic specificity for KK-LC-1 , wherein the TOR comprises

(c) an a chain comprising a sequence having at least 80%, at least 85%, at least 90%, at least 95% or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 87, and/or a p chain comprising a sequence having at least 80%, at least 85%, at least 90%, at least 95% or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 88; or

(e) an a chain comprising a sequence having at least 80%, at least 85%, at least 90%, at least 95% or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 91, and/or a p chain comprising a sequence having at least 80%, at least 85%, at least 90%, at least 95% or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 92; or

(f) an a chain comprising a sequence having at least 80%, at least 85%, at least 90%, at least 95% or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 93, and/or a p chain comprising a sequence having at least 80%, at least 85%, at

117 least 90%, at least 95% or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 94; or

(j) an a chain comprising a sequence having at least 80%, at least 85%, at least 90%, at least 95% or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 101 , and/or a p chain comprising a sequence having at least 80%, at least 85%, at least 90%, at least 95% or at least 99% sequence identity to the amino acid sequence of SEQ ID NO: 102; or

31. An isolated peptide having up to 18 amino acid residues and comprising or consisting of

(i) the amino acid sequence of any one of SEQ ID NOs: 1-16, or

118

32. The isolated peptide of claim 31 , wherein the peptide consists of from 13 to 16 amino acids.

33. The isolated peptide of claim 31 or claim 32, wherein the peptide consists of an amino acid sequence of any one of SEQ ID NOs: 1-16.

34. An isolated, ex vivo complex comprising:

(i) the amino acid sequence of any one of SEQ ID NOs: 1-16, or

(b) an MHC II molecule.

35. The isolated, ex vivo complex of claim 34, wherein the peptide consists of from 13 to 16 amino acids.

36. The isolated, ex vivo complex of claim 34 or claim 35, wherein the peptide consists of an amino acid sequence of any one of SEQ ID NOs: 1-16.

37. A nucleic acid sequence encoding an antigen recognizing construct or T cell receptor as defined in any one of claims 1 to 30 or a peptide as defined in any one of claims 31 to 33.

38. A vector comprising a nucleic acid sequence as defined in claim 37.

39. A host cell comprising the antigen recognizing construct or T cell receptor according to any one of claims 1 to 30, or the peptide according to any one of claims 31 to 33, or the complex according to any one of claims 34 to 36, or the nucleic acid sequence according to claim 37, or the vector according to claim 38.

40. The antigen recognizing construct or the T cell receptor according to any one of claims 1 to 30, or the peptide according to any one of claims 31 to 33, or the complex according to any one of claims 34 to 36, or the nucleic acid sequence according to claim 37, or the vector according to claim 38, or the host cell according to claim 39, for use in medicine.

119

41. The antigen recognizing construct or the T cell receptor according to any one of claims 1 to 30, or the peptide according to any one of claims 31 to 33, or the complex according to any one of claims 34 to 36, or the nucleic acid sequence according to claim 37, or the vector according to claim 38, or the host cell according to claim 39, for use in the prevention and/or treatment of a disease.

42. The antigen recognizing construct, or the T cell receptor, or the peptide, or the complex, or the nucleic acid sequence, or the vector, or the host cell according to claim 41 , wherein the disease is a malignant or benign tumor disease.

43. The antigen recognizing construct, or the T cell receptor, or the peptide, or the complex, or the nucleic acid sequence, or the vector, or the host cell according to claim 41 or claim 42, wherein the disease is a solid tumor that expresses Kita-Kyushu Lung Cancer Antigen 1 (KK-LC-1).

44. The antigen recognizing construct, or the T cell receptor, or the peptide, or the complex, or the nucleic acid sequence, or the vector, or the host cell according to claim 43, wherein the disease is an advanced-stage metastatic solid tumor that expresses Kita-Kyushu Lung Cancer Antigen 1 (KK-LC-1).

45. The antigen recognizing construct, or the T cell receptor, or the peptide, or the complex, or the nucleic acid sequence, or the vector, or the host cell according to any one of claims 31 to 44, wherein the disease is selected from the group consisting of cervical cancer, head cancer, neck cancer, melanoma, lung cancer, esophageal cancer, gastric cancer, breast cancer, ovarian cancer, mesothelioma cancer, bladder cancer, anal cancer, chondrosarcoma cancer, osteosarcoma cancer, sarcoma cancer, adenoma cancer, primitive neuroectodermal cancer (primitive neuroectodermal tumor (PNET)), and combinations thereof.

46. The antigen recognizing construct, or the T cell receptor, or the peptide, or the complex, or the nucleic acid sequence, or the vector, or the host cell according to claim 45, wherein the lung cancer is selected from the group consisting of squamous cell carcinoma of the lung, non-small cell lung cancer and small cell lung cancer.

47. The antigen recognizing construct, or the T cell receptor, or the peptide, or the complex, or the nucleic acid sequence, or the vector, or the host cell according to claim

120 45, wherein the breast cancer is selected from the group consisting of ductal breast cancer, tubular breast cancer, medullary breast cancer and combinations thereof.

48. The antigen recognizing construct, or the T cell receptor, or the peptide, or the complex, or the nucleic acid sequence, or the vector, or the host cell according to claim 45, wherein the gastric cancer is gastric adenocarcinoma cancer.

49. The antigen recognizing construct, or the T cell receptor, or the peptide, or the complex, or the nucleic acid sequence, or the vector, or the host cell according to claim 45, wherein the sarcoma cancer is selected from the group consisting of chondrosarcoma cancer, osteosarcoma cancer and combinations thereof.

50. The antigen recognizing construct, or the T cell receptor, or the peptide, or the complex, or the nucleic acid sequence, or the vector, or the host cell according to claim 45, wherein the adenoma cancer is selected from the group consisting of gastric adenocarcinoma, pancreatic adenocarcinoma and combinations thereof.

51. Use of the antigen recognizing construct or the T cell receptor according to any one of claims 1 to 30, or the peptide according to any one of claims 31 to 33, or the complex according to any one of claims 34 to 36, or the nucleic acid sequence according to claim 37, or the vector according to claim 38, or the host cell according to claim 39, for the manufacture of a medicament for treating a disease.

52. The use of the antigen recognizing construct or the T cell receptor, or the peptide, or the complex, or the nucleic acid sequence, or the vector, or the host cell, according to claim 51, wherein the disease is a malignant or benign tumor disease.

53. The use of the antigen recognizing construct or the T cell receptor, or the peptide, or the complex, or the nucleic acid sequence, or the vector, or the host cell, according to claim 51 or claim 52, wherein the disease is a solid tumor that expresses Kita-Kyushu Lung Cancer Antigen 1 (KK-LC-1).

54. The use of the antigen recognizing construct or the T cell receptor, or the peptide, or the complex, or the nucleic acid sequence, or the vector, or the host cell, according to claim 53, wherein the disease is an advanced-stage metastatic solid tumor that expresses Kita-Kyushu Lung Cancer Antigen 1 (KK-LC-1).

121

55. The use of the antigen recognizing construct or the T cell receptor, or the peptide, or the complex, or the nucleic acid sequence, or the vector, or the host cell, according to any one of claims 51 to 54, wherein the disease is selected from the group consisting of cervical cancer, head and neck cancer, melanoma, lung cancer, esophageal cancer, gastric cancer, breast cancer, ovarian cancer, mesothelioma cancer, bladder cancer, anal cancer, chondrosarcoma cancer, osteosarcoma cancer, sarcoma cancer, adenoma cancer, primitive neuroectodermal cancer (primitive neuroectodermal tumor (PNET)), and combinations thereof.

56. The use of the antigen recognizing construct or the T cell receptor, or the peptide, or the complex, or the nucleic acid sequence, or the vector, or the host cell, according to claim 55, wherein the lung cancer is selected from the group consisting of squamous cell carcinoma of the lung, non-small cell lung cancer and small cell lung cancer.

57. The use of the antigen recognizing construct or the T cell receptor, or the peptide, or the complex, or the nucleic acid sequence, or the vector, or the host cell, according to claim 55, wherein the breast cancer is selected from the group consisting of ductal breast cancer, tubular breast cancer, medullary breast cancer and combinations thereof.

58. The use of the antigen recognizing construct or the T cell receptor, or the peptide, or the complex, or the nucleic acid sequence, or the vector, or the host cell, according to claim 55, wherein the gastric cancer is gastric adenocarcinoma cancer.

59. The use of the antigen recognizing construct or the T cell receptor, or the peptide, or the complex, or the nucleic acid sequence, or the vector, or the host cell, according to claim 55, wherein the sarcoma cancer is selected from the group consisting of chondrosarcoma cancer, osteosarcoma cancer and combinations thereof.

60. The use of the antigen recognizing construct or the T cell receptor, or the peptide, or the complex, or the nucleic acid sequence, or the vector, or the host cell according to claim 55, wherein the adenoma cancer is selected from the group consisting of gastric adenocarcinoma, pancreatic adenocarcinoma and combinations thereof.

61. A method of treating a disease, comprising the step of administering a composition comprising the antigen recognizing construct or the T cell receptor according to any one of claims 1 to 30, or the peptide according to any one of claims 31 to 33, or the complex

122 according to any one of claims 34 to 36, or the nucleic acid sequence according to claim 37, or the vector according to claim 38, or the host cell according to claim 39.

62. The method of treating a disease according to claim 61 , wherein the disease is a malignant or benign tumor disease.

63. The method of treating a disease according to claim 61 or claim 62, wherein the disease is a solid tumor that expresses Kita-Kyushu Lung Cancer Antigen 1 (KK-LC-1).

64. The method of treating a disease according to claim 63, wherein the disease is an advanced-stage metastatic solid tumor that expresses Kita-Kyushu Lung Cancer Antigen 1 (KK-LC-1).

65. The method of treating a disease according to any one of claims 61 to 64, wherein the disease is selected from the group consisting of cervical cancer, head and neck cancer, melanoma, lung cancer, esophageal cancer, gastric cancer, breast cancer, ovarian cancer, mesothelioma cancer, bladder cancer, anal cancer, chondrosarcoma cancer, osteosarcoma cancer, sarcoma cancer, adenoma cancer, primitive neuroectodermal cancer (primitive neuroectodermal tumor (PNET)), and combinations thereof.

66. The method of treating a disease according to claim 65, wherein the lung cancer is selected from the group consisting of squamous cell carcinoma of the lung, non-small cell lung cancer and small cell lung cancer.

67. The method of treating a disease according to claim 65, wherein the breast cancer is selected from the group consisting of ductal breast cancer, tubular breast cancer, medullary breast cancer and combinations thereof.

68. The method of treating a disease according to claim 65, wherein the gastric cancer is gastric adenocarcinoma cancer.

69. The method of treating a disease according to claim 65, wherein the sarcoma cancer is selected from the group consisting of chondrosarcoma cancer, osteosarcoma cancer and combinations thereof.

123

70. The method of treating a disease according to claim 65, wherein the adenoma cancer is selected from the group consisting of gastric adenocarcinoma, pancreatic adenocarcinoma and combinations thereof.

71. A pharmaceutical composition comprising the antigen recognizing construct or the T cell receptor according to any one of claims 1 to 30, or the peptide according to any one of claims 31 to 33, or the complex according to any one of claims 34 to 36, or the nucleic acid sequence according to claim 37, or the vector according to claim 38, or the host cell according to claim 39.

72. A kit for use in medicine comprising the antigen recognizing construct or the T cell receptor according to any one of claims 1 to 30, or the peptide according to any one of claims 31 to 33, or the complex according to any one of claims 34 to 36, or the nucleic acid sequence according to claim 37, or the vector according to claim 38, or the host cell according to claim 39.

73. The kit according to claim 72, wherein the kit is a diagnostic kit for selecting a patient for treatment of a solid tumor, wherein cells of the tumor express the Kita-Kyushu Lung Cancer Antigen 1 (KK-LC-1).

74. A method of generating an antigen recognizing construct that binds a peptide selected from the group consisting of SEQ ID NOs: 1 to 16 with a determinable affinity, wherein the method comprises:

(i) immunization of a subject, and

(ii) isolating the antigen recognizing construct.

75. The method of generating an antigen recognizing construct according to claim 74, wherein step (i) comprising at least 7 immunization steps.

76. The method of generating an antigen recognizing construct according to claim 75, wherein each immunization step is selected from the group consisting of gene gun immunization, adenovirus immunization, and peptide immunization.

77. The method of generating an antigen recognizing construct according to any one of claim 74 to 76, wherein the antigen recognizing construct is a T cell receptor.

124

78. The method of generating an antigen recognizing construct according to any one of claims 74 to 76, wherein the method comprises immunization of the subject comprising 8 immunization steps.

79. The method of generating an antigen recognizing construct according to claim 78, wherein the first, second, third, fifth, seventh and eighth immunization of the subject are carried out with gene gun immunization, the fourth immunization is carried out with adenovirus immunization and the sixth immunization is carried out with peptide immunization.

125