Project/Area Number |
10671148
|
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 | Tohoku University |
Principal Investigator |
SHIIBA Ken-ichi Tohoku University , Postgraduate School of Medicin associate professor, 大学院・医学系研究科, 助教授 (90196345)
|
Co-Investigator(Kenkyū-buntansha) |
SEKI Naoko Kurume University, School Medicine, Research assoca, 医学部, 助手 (40226634)
MATSUNO Seiki Tohoku University , Postgraduate School of Medicin Professor, 大学院・医学系研究科, 教授 (80004737)
MIZOI Takayuki Tohoku University , Postgraduate School of Medicin Research Associate, 医学部・附属病院, 助手 (90271949)
SHICHIJO Shigeki Kurume University, School Medicine, associate professor, 医学部, 助教授 (30080592)
|
Project Period (FY) |
1998 – 2000
|
Project Status |
Completed (Fiscal Year 2000)
|
Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2000: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1999: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1998: ¥1,500,000 (Direct Cost: ¥1,500,000)
|
Keywords | gastric cancer / tumor rejection antigen / cancer vaccine / HLA / CTL / SART-1 / SART-2 / SART-3 |
Research Abstract |
Identification of genes coding for a new squamous cell carcinoma antigen, SART 1, 2, 3, recognized by the CTLs and identification of SART1, 2, 3-derived peptides capable of inducing allo-specific and tumor-specific CTLs in cancer patients : We have identified a SART1 gene coding tumor antigens recognized by HLA-A26-restricted CTLs and also by HLA-A-24-restricted CTLs. This SART1 gene encodes both the 125 kD of SART1_<800> antigen expressed in the nucleus and 43kD of SART1_<259> antigen expressed in the cytosol of the majority of SCCs. SART2 gene and SART3 gene were identified as new squamous cell carcinoma antigens recognized by cells of the HLA-A24-restricted and tumor-specific CTL line. Some of SART1, 2, 3- derived peptides induced allo-specific and peptide-specific CTLs from peripheral blood mononuclear cells in several cancer patients and healthy volunteers. Among these peptides, the two SART3 peptides possessed the ability to induce HLA-A2-restricted and tumor-specific CTLs from PBMC of cancer patients with various histological types and different HLA-A2 subtypes. These two peptides could be useful for specific immunotherapy of a relatively large number of HLA-A2+ cancer patients as well as HLA-A24+ cancer patients. Identification of genes coding for a gastric carcinoma antigen : We established several CTLs from tumor-infiltrating lymphocytes of gastric cancer patients. The allo-specific and tumor-specific reactivity of these CTLs were tested against COS-7 cells co-transfected with HLA-A2402 and cDNA derived from cDNA library of gastric cancer cell line, MKN-45. Subcloning of the gene responsible for CTL induction was performed and candidate peptide was identified and synthesized. However this peptide failed to induce CTLs from PBMC in either cancer patients or healthy volunteers.
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