| Project/Area Number |
11671348
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Thoracic surgery
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| Research Institution | University of Occupational and Environmental Health |
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Principal Investigator |
YOSHIMATSU Takashi (2000) UOEH, School of Medicine Research Associate, 医学部, 助手 (70279339)
小山 倫浩 (1999) 産業医科大学, 医学部, 助手 (00309965)
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| Co-Investigator(Kenkyū-buntansha) |
OSAKI Toshihiro UOEH, School of Medicine Assistant Professor, 医学部, 講師 (70248574)
吉松 隆 産業医科大学, 医学部, 助手 (70279339)
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2000: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1999: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Keywords | cytotoxic T cell / CD80 / lung cancer / 細胞障害性T細胞 |
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| Research Abstract |
Cytotoxic T lymphocytes (CTL) against human lung cancer cells have been hardly induced by a conventional method using tumor cell stimulation probably due to shortness of tumor antigens (TA) or costimulatory molecules such as CD80. We, therefore, investigated the potential of CD80-transfected tumor cells as stimulators on the in vitro induction of autologous tumor-specific CTL from regional lymph node lymphocytes in patients with lung cancer. Sixteen non-small cell lung cancer cell lines were established from surgical specimens of 550 cases. Eight cell lines out of 9 were successfully transduced with a plasmid constructed with expression vector pBj and human CD80 cDNA using a lipofection method. CD80-transfected tumor cells (CD80-AT) significantly augmented the proliferation of autologous lymphocytes from all cases as compared with non-transfected tumor cells (AT). Lymphocytes stimulated with CD80-AT exhibited substantial cytotoxicity against parental AT in all 8 cases tested. Using a limiting dilution method, CTL clones were established from 5 cases. The representative clone, D4/12 derived from lung adenocarcioma B203L, recognized not only AT but also HLA-A24-positive allogeneic tumor cell lines (lung adenocarcinoma, lung squamous cell carcinoma and melanoma). Analysis of the V alpha- and V beta -chains of the T cell receptor (TCR) expressed by this clone revealed usage of the V alpha20 and V beta30^*01. HLA-A24 is the most popular HLA typing in Japanese. These clones recognized HLA-A24-positive allogeneic tumor cell lines in spite of their histologic types. These results indicated that the tumor antigens recognized by these clones may widely express on HLA-A24 molecules and may be useful candidates for immunotherapy.
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