| 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)
辻村 邦夫 愛知県がんセンター, 腫瘍免疫学部, 主任研究員 (10227407)
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| Project Period (FY) |
2000 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥51,400,000 (Direct Cost: ¥51,400,000)
Fiscal Year 2004: ¥10,300,000 (Direct Cost: ¥10,300,000)
Fiscal Year 2003: ¥10,700,000 (Direct Cost: ¥10,700,000)
Fiscal Year 2002: ¥11,000,000 (Direct Cost: ¥11,000,000)
Fiscal Year 2001: ¥10,400,000 (Direct Cost: ¥10,400,000)
Fiscal Year 2000: ¥9,000,000 (Direct Cost: ¥9,000,000)
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| Keywords | Cancer / Cancer Antigen / Immune Response / Immunodiagnostics / Immunotherapy / Expression Cloning / Autoantibodv / cDNA Library / 抗体 / 免疫療法 / 発現クローニング / cDNA / 胃癌 / 乳癌 / 前立腺癌 / 大腸癌 / SEREX / 固型癌 |
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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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