EP2416807A1 - Novel strategies for improved cancer vaccines - Google Patents
Novel strategies for improved cancer vaccinesInfo
- Publication number
- EP2416807A1 EP2416807A1 EP10762283A EP10762283A EP2416807A1 EP 2416807 A1 EP2416807 A1 EP 2416807A1 EP 10762283 A EP10762283 A EP 10762283A EP 10762283 A EP10762283 A EP 10762283A EP 2416807 A1 EP2416807 A1 EP 2416807A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- cancer
- antigen
- antibody
- moiety
- seq
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Ceased
Links
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Classifications
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- A61K39/0005—Vertebrate antigens
- A61K39/0011—Cancer antigens
- A61K39/001102—Receptors, cell surface antigens or cell surface determinants
- A61K39/001124—CD20
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
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- C—CHEMISTRY; METALLURGY
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- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/2803—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily
- C07K16/2833—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily against MHC-molecules, e.g. HLA-molecules
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/2863—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against receptors for growth factors, growth regulators
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/2887—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against CD20
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/30—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
- C07K16/3007—Carcino-embryonic Antigens
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/44—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material not provided for elsewhere, e.g. haptens, metals, DNA, RNA, amino acids
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- A61K2039/60—Medicinal preparations containing antigens or antibodies characteristics by the carrier linked to the antigen
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- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/80—Vaccine for a specifically defined cancer
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
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- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/77—Internalization into the cell
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
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- C07K2319/00—Fusion polypeptide
- C07K2319/30—Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto
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- C07K2319/70—Fusion polypeptide containing domain for protein-protein interaction
Definitions
- the tumor-specific CD4+ T cells provides help and survival signals to tumor-specific CD8+ T cells and maintain CD8+ T-cell memory, which are essential for long-lasting anti-tumor immunity.
- the tumor protection efficacy can be augmented by combinational use of adoptive transfer of antigen-specific T cells, chemotherapy, monoclonal antibodies, and/or stem cell transplantation. Arrows with X represent inhibitory action, or negative effect.
- Exosomes are 30- to 100-nm diameter vesicles derived from a diverse range of cell types.
- DC-derived exosomes contain Ag-presenting, adhesion, and costimulatory molecules, which alone or in association with DCs can serve as a potent vaccine to stimulate strong CTL responses and induce antitumor immunity in different animal models (Chaput et al., 2004, J. Immunol. 172:2137-2146; Cho et al., 2005, Int. J. Cancer 114:613-622; Hao et al., 2007, Immunology 120:90-102).
- CD74 is a type-II integral membrane protein essential for proper MHC II folding and MHC II-CD74 complex targeting to endosomes (Stein et al., 2007, Clin. Cancer Res. 13:5556s-5563s; Matza et al., 2003, Trends Immunol. 24:264-268).
- CD20 amino acid sequences are known and readily available from a wide variety of species and can be incorporated into the anti-cancer vaccine complexes. Because the xenoantigen amino acid sequence is from a different species, the likelihood of self-tolerance of the host immune system is substantially reduced.
- Dendritic Cell Targeting Antibodies are known and readily available from a wide variety of species and can be incorporated into the anti-cancer vaccine complexes. Because the xenoantigen amino acid sequence is from a different species, the likelihood of self-tolerance of the host immune system is substantially reduced.
- PKA which plays a central role in the signal transduction pathway triggered by the binding of cAMP to the R subunits of PKA
- the structure of the holoenzyme consists of two catalytic subunits held in an inactive form by the R subunits (Taylor, J. Biol. Chem. 1989; 264:8443). Isozymes of PKA are found with two types of R subunits (RI and RII), and each type has ⁇ and ⁇ isoforms (Scott, Pharmacol. Ther. 1991; 50:123).
- Toxins of use may include ricin, abrin, alpha toxin, saporin, ribonuclease (RNase), e.g., onconase, DNase I, Staphylococcal enterotoxin-A, pokeweed antiviral protein, gelonin, diphtheria toxin, Pseudomonas exotoxin, and Pseudomonas endotoxin.
- RNase ribonuclease
- Such a tail can be a polymer such as a polylysine, polysaccharide, or other derivatized or derivatizable chains having pendant groups to which can be bound chelating groups such as, e.g., ethyl enediaminetetraacetic acid (EDTA), diethylenetriaminepentaacetic acid (DTPA), porphyrins, polyamines, crown ethers, bis-thiosemicarbazones, polyoximes, and like groups known to be useful for this purpose.
- EDTA ethyl enediaminetetraacetic acid
- DTPA diethylenetriaminepentaacetic acid
- porphyrins porphyrins
- polyamines e.g., ethyl enediaminetetraacetic acid (EDTA), diethylenetriaminepentaacetic acid (DTPA), porphyrins, polyamines, crown ethers, bis-thiosemicarbazones, polyoximes,
- the active ingredient can be in powder form for constitution with a suitable vehicle, e.g., sterile pyrogen-free water, before use.
- a suitable vehicle e.g., sterile pyrogen-free water
- Additional pharmaceutical methods may be employed to control the duration of action of the vaccine construct.
- Control release preparations can be prepared through the use of polymers to complex or adsorb the vaccine construct.
- biocompatible polymers include matrices of poly(ethylene-co-vinyl acetate) and matrices of a polyanhydride copolymer of a stearic acid dimer and sebacic acid. Sherwood et al, Bio/Technology 10: 1446 (1992).
- Additional hyperproliferative diseases, disorders, and/or conditions include, but are not limited to, progression, and/or metastases of malignancies and related disorders such as leukemia (including acute leukemias (e.g., acute lymphocytic leukemia, acute myelocytic leukemia (including myeloblastic, promyelocytic, myelomonocytic, monocytic, and erythroleukemia)) and chronic leukemias (e.g., chronic myelocytic (granulocytic) leukemia and chronic lymphocytic leukemia)), polycythemia vera, lymphomas (e.g., Hodgkin's disease and non-Hodgkin's disease), multiple myeloma, Waldenstrom's macroglobulinemia, heavy chain disease, and solid tumors including, but not limited to, sarcomas and carcinomas such as fibrosarcoma, myxosarcoma, lipos
- kits containing components suitable for treating a disease in a patient.
- Exemplary kits may contain at least one or more vaccine constructs as described herein.
- a device capable of delivering the kit components through some other route may be included.
- One type of device, for applications such as parenteral delivery, is a syringe that is used to inject the composition into the body of a subject. Inhalation devices may also be used.
- a therapeutic agent may be provided in the form of a prefilled syringe or autoinjection pen containing a sterile, liquid formulation or lyophilized preparation.
- TF2 was purified to near homogeneity by IMP 291 affinity chromatography (not shown).
- IMP 291 is a synthetic peptide containing the HSG hapten to which the 679 Fab binds (Rossi et al., 2005, Clin Cancer Res 11 :7122s-29s).
- SE-HPLC analysis of the IMP 291 unbound fraction demonstrated the removal of a 4 , a 2 and free kappa chains from the product (not shown).
- C H3 -AD2-IgG-hLLl (anti-CD74) is produced as described in Examples 2 and 3.
- the construct comprises an AD2 moiety attached to the C-terminal end of each heavy chain of the hLLl IgG.
- DDD2-mCD20(136-178) is produced as described in Example 4.
- a DNL reaction is performed by mixing hLLl IgG- AD2 and DDD2-mCD20(136-178) in PBS containing 1 mM reduced glutathione. On the next day oxidized glutathione is added to a final concentration of 2 mM and the reaction mixture is purified on a Protein A column 24 h later.
- two copies of the DDD2-mCD20 are attached to each AD2 moiety, resulting in a DNL complex comprising one hLLl IgG moiety and four mCD20 xenoantigen moieties.
- Example 8 In vitro properties of 74-mCD20 - Induction of hCD20-specific immunity by 74-mCD20 in human PBMCs
- 74-mCD20 or Ml-mCD20 are labeled with a ZENONTM ALEXA FLUOR® 488 human IgG labeling kit (INVITROGEN®) following the manufacturer's instructions.
- the labeled preparations are used to stain the human PBMCs as described below..
- Human PBMCs isolated from buffy coat using FICOLL-P AQUETM are treated with human FcR blocking Reagent (Miltenyi Biotec, 1 :20 dilution) at 4°C for 10 min. The washed cells are stained with specifically labeled mAbs and analyzed by flow cytometry (FACSCALIBUR®).
- NOD/SCID mice are also used for evaluating the therapeutic effect by co- engraftment of tumor cells and hPBMC. By carefully adjusting the cell numbers infused, this model can support both tumor growth and hPBMC engraftment, and has been used for testing the effect of an in vivo vaccine targeting DC-SIGN.
- a DDD2 conjugated PAP xenoantigen is generated from murine prostatic acid phosphatase according to the method of Example 4.
- the efficacy of dendritic cell based vaccination with a PAP xenoantigen has been previously disclosed (Fong et al. J Immunol 2001, 167:7150-56).
- a DDD2-mPAP-pdHL2 expression vector is constructed as described in Example 4 and the DDD2-mPAP xenoantigen fusion protein is expressed in cell culture according to Example 4.
- the murine prostatic acid phosphatase sequence is disclosed, for example, in the NCBI database at Accession No. AAF23171.
- a DDD2-mPAP-6His fusion protein (“6His" disclosed as SEQ ID NO: 28) is expressed and purified by immobilized metal affinity chromatography (IMAC) as described in Example 4.
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US12/544,476 US7901680B2 (en) | 2005-10-19 | 2009-08-20 | Dock-and-lock (DNL) vaccines for cancer therapy |
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WO2010022225A1 (en) * | 2008-08-20 | 2010-02-25 | Ibc Pharmaceuticals, Inc. | Dock-and-lock (dnl) vaccines for cancer therapy |
Non-Patent Citations (6)
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CHANG C-H ET AL: "The Dock and Lock Method: A Novel Platform Technology for Building Multivalent, Multifunctional Structures of Defined Composition with Retain Bioactivity", CLINICAL CANCER RESEARCH, THE AMERICAN ASSOCIATION FOR CANCER RESEARCH, US, vol. 13, no. 18 SUPPL, 15 September 2007 (2007-09-15), pages 5586S-5591S, XP008123543, ISSN: 1078-0432, DOI: 10.1158/1078-0432.CCR-07-1217 * |
KIRSHNER JULIA ET AL: "A unique three-dimensional model for evaluating the impact of therapy on multiple myeloma", BLOOD, vol. 112, no. 7, October 2008 (2008-10), pages 2935-2945, XP2674576, ISSN: 0006-4971 * |
KRETZ-ROMMEL ANKE ET AL: "In vivo targeting of antigens to human dendritic cells through DC-SIGN elicits stimulatory immune responses and inhibits tumor growth in grafted mouse models", JOURNAL OF IMMUNOTHERAPY, LIPPINCOTT WILLIAMS & WILKINS, HAGERSTOWN, MD, US, vol. 30, no. 7, 1 October 2007 (2007-10-01), pages 715-726, XP009094216, ISSN: 1524-9557 * |
ROSSI E A ET AL: "Stably Tethered Multifunctional Structures of Defined Composition Made by the Dock and Lock Method for Use in Cancer Targeting", PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES, NATIONAL ACADEMY OF SCIENCES, vol. 103, no. 18, 2 May 2006 (2006-05-02), pages 6841-6846, XP008123542, ISSN: 0027-8424, DOI: 10.1073/PNAS.0600982103 [retrieved on 2006-04-24] * |
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TITZER S ET AL: "Vaccination of multiple myeloma patients with idiotype-pulsed dendritic cells: immunological and clinical aspects.", BRITISH JOURNAL OF HAEMATOLOGY MAR 2000 LNKD- PUBMED:10792287, vol. 108, no. 4, March 2000 (2000-03), pages 805-816, XP2674551, ISSN: 0007-1048 * |
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