2004 Fiscal Year Final Research Report Summary
Identification of Cancer Antigens by SEREX, an Expression Cloning Method.
| Project/Area Number |
12213165
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| Research Category |
Grant-in-Aid for Scientific Research on Priority Areas
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| Allocation Type | Single-year Grants |
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| Review Section |
Biological Sciences
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| Research Institution | RIKEN (2001-2004)
Aichi Cancer Center Research Institute (2000) |
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Principal Investigator |
OBATA Yuichi RIKEN Department of Biological Systems, Chief Scientist, リソース基盤開発部・基盤開発部長(主任研究員待遇) (30177290)
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| Co-Investigator(Kenkyū-buntansha) |
SAKAMOTO Junichi Kyoto University School of Public Health, Department of Epidemiological & Clinical Research Information Management, Professor, 医学部・疫学研究情報管理学講座, 教授 (70196088)
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| Project Period (FY) |
2000 – 2004
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| Keywords | Cancer / Cancer Antigen / Immune Response / Immunodiagnostics / Immunotherapy / Expression Cloning / Autoantibodv / cDNA Library |
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| Research Abstract |
The goals of this study are identification and selection of antigenic molecules that are recognized by the immune system of cancer patient and are useful in clinical setting. To achieve these goals, an expression cloning method named SEREX (SErological identification of antigens by REcombinant EXpression cloning) has been used. In SEREX, an expression cDNA library constructed from cancer specimen was screened with the cancer patient's own serum. cDNA clones that produce antigenic proteins are identified on the basis of reaction with high titered IgG antibodies in the autologous serum. So far, 5 gastric cancers, 3 prostate cancers, 2 breast cancers, 2 colon cancers, 2 sarcomas and 1 lung cancer have been screened and over 700 antigens have been identified. The immune system of cancer patients was surprisingly very active, contrary to the common belief that the immune system of cancer patients is suppressed or non-responsive. Most antigens identified in this study are derived from normal
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proteins without any mutation and are expressed ubiquitously in a wide range of normal tissues. Thus, it was suggested that development of cancer elicits the immune response as "Danger Signal" to the body.
To select antigens that can be useful in immunodiagnostics and immunotherapy of cancer, all antigens identified in this study were examined for cancer specificity of their expression and for cancer patient specific immune response against them. Approximately 20 candidate antigens have been selected each from gastric, prostate and breast cancer. Examples are E-cadherin/Novel Gene fusion protein, Hsp60 and Novel Gene YS278 in gastric cancers, SSX-2, NY-BR-1 and Hsp105 in breast cancers, and HERV-K, NY-BR-1 and Fanconi Anemia Group A in prostate cancers. Among these, most promising antigens are HERV-K, human endogenous retroviral protein that is known to be expressed restrictedly in prostate cancers and germ cell tumors, NY-BR-1 that is a differentiation antigen of normal breast but aberrantly expressed in breast and prostate cancers and SSX-2, a member of Cancer Testis (CT) antigens that are considered as ideal antigens as targets for cancer immunotherapy. Development of an immunodiagnostic method for cancer by measuring amounts of antibodies against these antigens as well as induction of cytotoxic T cell against these promising antigens are now being tried. Less
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[Journal Article] Clonal expansion of double-positive intraepithelial lymphocytes by MHC class I-related chain a expressed in mouse small intestinal epithelium.2003
Author(s)
Park, E.J.Takahashi, I., Ikeda, J,.Kawahara, K., Okamoto, T., Kweon, M.-N., Fukuyama, S., Groh, V., Spies, T., Obata.Y., Miyazaki, J.-I., Kiyono, H
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Journal Title
J.Immunol. 171
Pages: 4131-4139
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Expression of cancer/testis (CT) antigens in lung cancer.2003
Author(s)
Tajima, K, Obata.Y., Tamaki, H., Yoshida, M., Chen, Y-T., Scanlan, M.J., Old, L.J., Kuwano, H., Takahashi, T., Takahashi, T., Mitsudomi, T.
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Journal Title
Lung Cancer 42
Pages: 23-33
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Immunomic analysis of human sarcoma.2003
Author(s)
Lee, S-Y., Obata.Y., Yoshida, M., Stockert, E., Williamson, B., Jungbluth, A.A., Chen, Y-T., Old, L.J., Scanlan, M.J.
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Journal Title
Proc.Natl.Acad.Sci, USA. 100
Pages: 2561-2656
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Targeted cloning of cytotoxic T cells specific for minor histocompatibility antigens restricted by HLA class I molecules of interest.2002
Author(s)
Akatsuka, Y., Kondo, E., Taji, H., Morishima, Y., Yazaki, M., Obata.Y., Kodera, Y., Riddell, S.R., Takahashi, T.
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Journal Title
Transplantation. 74
Pages: 1773-1780
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Tumor-infiltrating B lymphocytes as a potential source of identifying tumor antigen in human lung cancer.2002
Author(s)
Yasuda, M., Takenoyama, M., Obata.Y., Sugaya, M., So, T., Hanagiri, T., Sugio, K., Yasumoto K
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Journal Title
Cancer Res. 62
Pages: 1751-1756
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] The binding of thymus leukemia (TL) antigen tetramers to normal intestinal intraepithelial lymphocytes and thymocytes.2001
Author(s)
Tsujimura, K., Obata.Y., Matsudaira, Y., Ozeki, S., Yoshikawa, K., Saga, S., Takahashi, T.
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Journal Title
J.Immunol. 167
Pages: 759-764
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] SEREX analysis of gastric cancer antigens.2000
Author(s)
Obata.Y., Takahashi, T., Sakamoto, J., Tamaki, H., Tominaga, S., Hamajima, N., Chen, Y.-T., Old, L.J.
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Journal Title
Cancer Chemother. Pharmacol. 46 (suppl)
Pages: S37-S42
Description
「研究成果報告書概要(欧文)」より
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