| Project/Area Number |
14370396
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Digestive surgery
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| Research Institution | Kurume University |
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Principal Investigator |
YAMANA Hideaki Kurume University, Medicine, Professor, 医学部, 教授 (30140669)
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| Co-Investigator(Kenkyū-buntansha) |
TOH Uhi Kurume University, Medicine, Assistant, 医学部, 助手 (60268901)
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| Project Period (FY) |
2002 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥13,800,000 (Direct Cost: ¥13,800,000)
Fiscal Year 2004: ¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 2003: ¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2002: ¥7,300,000 (Direct Cost: ¥7,300,000)
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| Keywords | advanced cancers / Phase I / II trial / activated T lymphocytes / cancer peptide vaccine / gene expression / regulatory T cell / CD4; / CD25+ T cell / proteasome inhibitor / CD4+CD25+T cell / Chemothrapy / 第II相試験 / IL-2 receptor / 抗IL-2 receptor抗体 / TRAIL / TRAIL receptor / Phase II Trial / IL-2 / 自己癌細胞 / 癌局所移入 / 有害事象 / 抗腫瘍効果 |
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| Research Abstract |
We are performing adoptive immunotherapy using autologous cancer specific cytotoxic T lymphocytes (CTLs). In this clinical trial, peripheral blood mononuclear cells (PBMC) obtained from advanced cancer patient were cultured for about 14 days under the addition of IL-2 (100U/ml) and patient's irradiated tumor cells. Following the cultivation, predominant CTLs including NK cells and LAK cells were recognized in most PBMC. Further more, we are performing phase I/II trial for advanced or recurrent cancer patients using CTL precursor-oriented cancer vaccine. For cancer samples obtained from these patients, gene analysis using DNA tip was planned to define effective cases of immunotherapy prior to treatment. In this study, II cancer samples were stocked, 6 were effective case samples and 5 were non effective case samples. However we have failed to stock cancer samples in many cases due to no tumor lesion or rejection of gene analysis.
In the fundamental studies on regulatory T cell analysis, CD4+/CD25+ T-cells were dominant in cultured lymphocytes more than 14 days. These regulatory T-cells were reduced by in vitro treatment of anti-IL-2 receptor α antibody. By this treatment, production of TGF-β was also reduced. We performed further fundamental study on proteasome inhibitor (PI) to improve the effect of cancer immunotherapy. By the PI treatment of cancer cells with weak expression of TRAIL receptor, TRAIL receptor was markedly expressed and TRAIL activity was significantly improved.
From these results, we have to control regulatory T-cell and TRAIL activity to improve the clinical effect of cancer immunotherapy. Further we will continue the storage of cancer samples to investigate gene analysis by DNA tip.
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