EP1194542A1 - Clonage d'adn complementaire de 5, 8, 9 et 11 de mage et leur utilisation dans le diagnostic du cancer - Google Patents
Clonage d'adn complementaire de 5, 8, 9 et 11 de mage et leur utilisation dans le diagnostic du cancerInfo
- Publication number
- EP1194542A1 EP1194542A1 EP00912112A EP00912112A EP1194542A1 EP 1194542 A1 EP1194542 A1 EP 1194542A1 EP 00912112 A EP00912112 A EP 00912112A EP 00912112 A EP00912112 A EP 00912112A EP 1194542 A1 EP1194542 A1 EP 1194542A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- mage
- seq
- nucleic acid
- acid molecule
- isolated
- 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.)
- Withdrawn
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
- C07K14/4701—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals not used
- C07K14/4748—Tumour specific antigens; Tumour rejection antigen precursors [TRAP], e.g. MAGE
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
Definitions
- This invention relates to nucleic acid molecules which are members of the MAGE
- MHC or HLA molecules form complexes with MHC or HLA molecules, fusion proteins, polytopes, and so forth.
- HLAs human immunoglobulins
- MAGE-B cluster of genes are referred to as the MAGE-B cluster of genes. Additional MAGE family members have been located at region q26, and have been named
- RT-PCR reverse transcription-polymerase chain reaction
- Testis expresses all MAGE-A
- lymphocyte-tumor cell culture The lymphocyte-tumor cell culture.
- Figure 1 presents exon/intron structures of MAGE genes, including for MAGE-
- the first pair is described by De Plaen, et al.,
- CTGGGTAAAG ACTCACTGTC TGG (SEQ ID NO: 2)
- SEQ ID NOS: 3&4 correspond to sequences complementary to the last exon of
- the frequency of expression of MAGE-Al was determined using cell line LB 11 -
- ID NOS: 3 & 4 had been used as primers. All corresponded to MAGE-Al 0.
- a cDNA library was prepared from a MAGE-A positive sample, following
- samples were homogenized in guanidine thiocyanate to form a lysate
- poly(A)+ RNA was converted to cDNA with an oligo(dT) primer which contained a Notl restriction site.
- the resulting cDNA was ligated to BstXI adaptors, digested with Notl,
- microwell plate 100 ⁇ ls per microwell. Two or three plates were seeded from every
- pooled to obtain 20 different pools from every plate (i.e., 8 pools from lines, and 12 pools
- the PCR assays were carried out on both the living and frozen bacteria, with the
- the number of positive wells in a plate was less than 20%.
- the likelihood of having a single clone in a well should be 90% or greater. Limiting dilution could be carried out to the point where less than 10% of the wells are positive,
- MZ2-MEL43 1/5,000 ( 18) 1/6 200 (16) 1/5,000 (20) 0/100 000 1/500 000 1/5,000 (20) 0/100,000 0/100 000 0/100,000 1/6 600 (15) 0/100 000 0/ 100 000
- TT-THYR 1/21 600 (5) 1/ 12 000 (9) 1/15,400 (7) 1/6 300 (17) 0/108 000 1/18,000 (6) 0/108 000 1/12,000 (9) 0/800 000 0/108,000 0/108,000 1/12,000 (9)
- the first line gives the abundance of cloned MAGE-A cDNAs in the library calculated, according to the Poisson distribution, from 10 the number of microwel Is scored positive by the PCR assay (number in brackets)
- One microwell contained 350 to 860 different clones.
- the second line gives the results of PCR assays performed on uncloned cDNAs
- the level of expression evaluated by the Intensity of the band obtained by separating PCR products in agarose gels is represented +++, +++, ++, + or +/- Absence of product is indicated by -
- the first estimation was obtained with previously described primers (De Plaen et al , 1994)
- a second one presented in brackets for genes MAGE-Al , 9 and 10 was obtained with recently developed pairs of primers
- primers and a level of expression was estimated based upon intensity of banding on an
- the limiting dilution assay revealed a level of expression of MAGE- A 10 which was
- SEQ ID NOS: 7 and 8 are better at determining expression levels.
- MAGE-A 10 showed the highest level of expression
- A1-A7 A9 and A12 were not found at all among 230,000 clones analyzed.
- the method involves preparing cDNA from a sample,
- transformants/transfectants These cells are then divided into a plurality of samples of
- the number of positive samples should be less than or equal to 20% of
- the frequency of each MAGE cDNA is determined.
- the method is carried out by distributing the samples in a predetermined
- cDNA had not been isolated previously, and is a further feature of the invention, i.e., isolated
- nucleic acid molecules such as the one
- nucleic acid molecules i.e., all of the nucleic acid molecules described herein, can be used
- expression vectors which comprise the nucleic acid molecule operably linked to a
- nucleic acid molecules can also be used both diagnostically and therapeutically.
- a sample such as a cell containing sample, a cell lysate, etc.
- oligomer for expression of the nucleic acid molecules described herein, using oligomer
- MAGE nucleic acid molecule of interest For example SEQ ID NO: 9 and or SEQ ID NO:
- SEQ ID NO: 11 and/or 12 can be used to determine
- peptides consisting of from about 8 to about 25 amino acids
- Such peptides are specific binders for MHC molecules, such as
- HLA molecules such as HLA-Al, A2, A3,
- amino acid sequences are set out at SEQ ID NOS:21-24, where SEQ ID NO:21 is that for
- SEQ ID NO:22 is that for MAGE A8
- SEQ ID NO:23 is that for MAGE A9
- SEQ ID NO:24 is that for MAGE Al 1 :
- compositions based upon these molecules are also a part of the invention, such as
- compositions containing a MAGE protein in accordance with the invention and a
- a pharmaceutically acceptable adjuvant such as a cytokine, an interleukin (e.g., IL-2JL-4, IL-
- dendritic cells which may be treated to be rendered non-proliferative, etc.
- peptides or proteins may be used in the form of appropriate compositions, such as in liposome
- compositions based compositions. Also a part of the invention are isolated cytolytic T cell lines which are
- a further aspect of the invention are so-called "mini genes" which carry information
- Mini genes can be designed which encode one or more antigenic peptides, and
- vaccinia or adenoviruses See, e.g., Zajac, et al, Int. J. Cancer 71 : 496 (1997), incorporated
- recombinant vectors such as recombinant vaccinia virus vectors
- fusion proteins can be constructed so as to produce fusion proteins.
- fusion proteins can be constructed where one portion of the fusion protein is the desired tumor rejection antigen precursor, or
- tumor rejection antigen and additional protein or peptide segments can be included.
- reporter proteins or peptides i.e., proteins or peptides
- fluoresence protein Additional reporter proteins include, but are by no means limited to,
- proteins such as ⁇ galactosidase, luciferase, dhfr, and "eGFP", or enhanced green fluorescent
- GFP and eGFP
- the fusion protein can include more than one tumor rejection antigen,
- proteins or peptides which facilitate the delivery of
- peptides are well known to the art, and need not be elaborated herein.
- Such cells may be, e.g., any type of eukaryotic cell, with human cells being especially preferred. Such cells can then be used, e.g., to
- tumor rejection antigen precursors or tumor rejection antigens are produced. They can also be produced tumor rejection antigen precursors or tumor rejection antigens. They can also be produced tumor rejection antigen precursors or tumor rejection antigens. They can also be produced tumor rejection antigen precursors or tumor rejection antigens. They can also be produced tumor rejection antigen precursors or tumor rejection antigens. They can also be produced tumor rejection antigen precursors or tumor rejection antigens. They can also be produced tumor rejection antigen precursors or tumor rejection antigens. They can also be produced tumor rejection antigen precursors or tumor rejection antigens. They can also be produced tumor rejection antigen precursors or tumor rejection antigens. They can also be produced tumor rejection antigens. They can also be produced tumor rejection antigens. They can also be produced tumor rejection antigen precursors or tumor rejection antigens. They can also be produced tumor rejection antigens. They can also be produced tumor rejection antigens. They can also be produced tumor rejection antigens. They can also be produced tumor rejection antigens. They can also be produced tumor rejection antigens.
- MHC molecules and tumor rejection antigens This can be done simply by contacting the
- transfected cells to a source of T cells, such as a blood sample, so as to provoke the
- TRAs i.e., tumor rejection antigens
- Such cells when rendered non-proliferative, can also be used as
- the vectors can be any type of T cell response in vivo, as is shown herein.
- the vectors can be any type of T cell response in vivo, as is shown herein.
- the vectors can be any type of T cell response in vivo, as is shown herein.
- the vectors can be any type of T cell response in vivo, as is shown herein.
- the vectors can be any type of T cell response in vivo, as is shown herein. Similarly, the vectors can be any type of T cell response in vivo, as is shown herein. Similarly, the vectors can be any type of T cell response in vivo, as is shown herein. Similarly, the vectors can be any type of T cell response in vivo, as is shown herein. Similarly, the vectors can be any type of T cell response in vivo, as is shown herein. Similarly, the vectors can be any type of T cell response in vivo, as is shown herein. Similarly, the vectors can be any type of
- T cell used as vaccine materials per se, and can be administered to a patient in need of a T cell
- cells generated ex vivo can also be used to treat patients.
- the peptides may be combined with peptides from other tumor rejection antigens to
- peptides include those listed in U.S. Patent Application Serial
- Polytopes are groups of two or more potentially immunogenic or immune stimulating
- peptides can be joined together directly, or via the use of flanking sequences.
- polytopes can be introduced as polypeptide structures, or via
- nucleic acid delivery systems To elaborate, the art has many different ways available to introduce DNA encoding an individual epitope, or a polytope such as is discussed
- Adenovirus pox-virus, Ty-virus like particles, plasmids, bacteria, etc.
- a feature of the invention is the use of these peptides to determine the presence
- HLA molecules can be "lysed" by adding the peptides of the invention to positive
- TNF production etc. or any other of the methods by which T cell activity is
- TILs lymphocytes
- HLA positive cells to a sample, and determining lysis of the HLA positive cells via, e.g., 51 Cr
- CTL may be detected by ELISPOT analysis.
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Genetics & Genomics (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Molecular Biology (AREA)
- Zoology (AREA)
- Biotechnology (AREA)
- General Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Health & Medical Sciences (AREA)
- Wood Science & Technology (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Physics & Mathematics (AREA)
- Microbiology (AREA)
- Plant Pathology (AREA)
- Immunology (AREA)
- Toxicology (AREA)
- Gastroenterology & Hepatology (AREA)
- Medicinal Chemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
Abstract
L'invention concerne des molécules d'ADN complémentaire isolées et déterminées grâce à une méthode élaborée pour faciliter le niveau d'expression génique. L'invention concerne également des protéines et des peptides obtenus sur la base de ces molécules d'ADN complémentaire, ainsi que différentes utilisations diagnostiques et thérapeutiques de ces matières.
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US26097899A | 1999-03-02 | 1999-03-02 | |
PCT/US2000/005346 WO2000052163A1 (fr) | 1999-03-02 | 2000-03-01 | Clonage d'adn complementaire de 5, 8, 9 et 11 de mage et leur utilisation dans le diagnostic du cancer |
US260978 | 2001-01-12 |
Publications (1)
Publication Number | Publication Date |
---|---|
EP1194542A1 true EP1194542A1 (fr) | 2002-04-10 |
Family
ID=22991462
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP00912112A Withdrawn EP1194542A1 (fr) | 1999-03-02 | 2000-03-01 | Clonage d'adn complementaire de 5, 8, 9 et 11 de mage et leur utilisation dans le diagnostic du cancer |
Country Status (7)
Country | Link |
---|---|
EP (1) | EP1194542A1 (fr) |
JP (1) | JP2003512814A (fr) |
KR (1) | KR20020011967A (fr) |
AU (1) | AU3389500A (fr) |
CA (1) | CA2366059A1 (fr) |
NZ (1) | NZ513739A (fr) |
WO (1) | WO2000052163A1 (fr) |
Families Citing this family (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2007053956A1 (fr) | 2005-11-14 | 2007-05-18 | Universite Laval | Antigene cancereux mage-a9 et ses utilisations |
SG11201913302SA (en) | 2017-07-07 | 2020-01-30 | Immatics Biotechnologies Gmbh | Novel peptides and combination of peptides for use in immunotherapy against lung cancer, including nsclc, sclc and other cancers |
US10800823B2 (en) | 2017-07-07 | 2020-10-13 | Immatics Biotechnologies Gmbh | Peptides and combination of peptides for use in immunotherapy against lung cancer, including NSCLC, SCLC and other cancers |
FR3087448B1 (fr) | 2018-10-23 | 2023-10-13 | Pdc Line Pharma | Lignee pdc modifiee pour secreter une cytokine |
TW202039535A (zh) | 2018-12-18 | 2020-11-01 | 德商英麥提克生物技術股份有限公司 | B*08限制肽和肽組合物抗癌免疫治療和相關方法 |
Family Cites Families (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5612201A (en) * | 1991-05-23 | 1997-03-18 | Ludwig Institute For Cancer Research | Isolated nucleic acid molecules useful in determining expression of a tumor rejection antigen precursor |
US5342774A (en) * | 1991-05-23 | 1994-08-30 | Ludwig Institute For Cancer Research | Nucleotide sequence encoding the tumor rejection antigen precursor, MAGE-1 |
-
2000
- 2000-03-01 EP EP00912112A patent/EP1194542A1/fr not_active Withdrawn
- 2000-03-01 NZ NZ513739A patent/NZ513739A/xx not_active Application Discontinuation
- 2000-03-01 WO PCT/US2000/005346 patent/WO2000052163A1/fr not_active Application Discontinuation
- 2000-03-01 KR KR1020017011090A patent/KR20020011967A/ko not_active Application Discontinuation
- 2000-03-01 JP JP2000602775A patent/JP2003512814A/ja active Pending
- 2000-03-01 CA CA002366059A patent/CA2366059A1/fr not_active Abandoned
- 2000-03-01 AU AU33895/00A patent/AU3389500A/en not_active Abandoned
Non-Patent Citations (1)
Title |
---|
See references of WO0052163A1 * |
Also Published As
Publication number | Publication date |
---|---|
KR20020011967A (ko) | 2002-02-09 |
AU3389500A (en) | 2000-09-21 |
WO2000052163A1 (fr) | 2000-09-08 |
CA2366059A1 (fr) | 2000-09-08 |
JP2003512814A (ja) | 2003-04-08 |
NZ513739A (en) | 2001-09-28 |
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