1998 Fiscal Year Final Research Report Summary
Cloning of the HLA A2402 restricted rejection antigen gene in colorectal cancers
Project/Area Number |
09671348
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Digestive surgery
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Research Institution | Kurume University |
Principal Investigator |
SASATOMI Teruo Kurume Univ.Sch.of Med.Dept.of Surgery, 医学部, 助手 (20196190)
|
Co-Investigator(Kenkyū-buntansha) |
ITOH Kyogo Kurume Univ.Sch.of Med.Dept.of Immunology, Professor, 医学部, 教授 (50125499)
|
Project Period (FY) |
1997 – 1998
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Keywords | tumor rejection antigen / gene cloning / CTL / HLA restriction |
Research Abstract |
We recently reported the tumor-rejection antigen gene SART1 encoding both the SART1 259 antigen expressed in the cytosol of epithelial cancers, and the SAR_<800> antigen expressed in the nucleus of the majority of proliferating cells. This study investigated the expression of these tumor antigens to explore a potential molecule for specific immunotherapy of colorectal cancer patients. SART1 antigens were investigated by Western blotting in 6 colorectal cancer cell lines and in 33 colorectal cancer tissues. The cancer cell lines were tested for their ability to stimulate 1FN-g production by the HLA-A24-restricted and SART1 specific cytotoxic T lymphocytes (CTLs). PBMC obtained from HLA A-24 positive donor were stimulated in vitro with the SART- 1 peptide that is recognized by the HLA-A24 restricted CTLs. And we investigated capability of the induction of GTL.by these peptide The SART1_<259> antigen was detected in the cytosol of 4 of 6 cancer cell lines, and 13 of 33 (39%) cancer tissues, and 0 of 7 non-tumorous colorectal tissues. The SART1_<800> antigen was expressed in the nucleus of all the colorectal cancer cell lines, 18 of 33 (55%) cancer tissues, and 0 of 7 non-tumorous tissues. The TLA-A24 SART-1_<259>' cancer cells were recognized by the HLA-A 24-restricted and SART1 specific CTLs. The stimulated PBMC recognized the HLA-A24 and SART-1_<259> colorectal cancer cells. The SART- 1 peptide that is recognized by the HLA-A24 restricted CTLs has the ability to induce GTLs in PBMCs. These results suggest that the SART1259 antigen could be an appropriate target moleculefor specificimmunotherapy of approximately4O% ofthe HLA-A24' patients with colorectal cancer.
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