Development of novel combined immunotherapy using in silico screening system
| Project/Area Number |
18K07331
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 50020:Tumor diagnostics and therapeutics-related
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| Research Institution | Keio University |
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Principal Investigator |
Matsushita Maiko 慶應義塾大学, 薬学部(芝共立), 准教授 (10327520)
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| Co-Investigator(Kenkyū-buntansha) |
服部 豊 慶應義塾大学, 薬学部(芝共立), 教授 (20189575)
河上 裕 慶應義塾大学, 医学部(信濃町), 特任教授 (50161287)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 多発性骨髄腫 / 免疫学的細胞死 / 複合免疫療法 / 免疫増強薬 / 膵がん |
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| Outline of Final Research Achievements |
In this sudy, we tried to identify immunomodulatory drugs for effectice combined immunotherapy against myeloma and other cancers, which are poorly responsive to immune-chkeckpoint inhibitors. We found that proteasome inhibitors could highly induce immunogenic cell death (ICD) in myeloma cells in vitro. Myeloma cells treated with these drugs could enhance maturation of dendritic cells and expansion of T cells. In addition, we isolated cytotoxic T cells against a novel tumor antigen expressed in various cancers, including myelama or pancreatic cancer. We successfully cloned T cell receptor genes and generated human T cell lines tranduced with these TCR genes. Combination thrapy of proteasome inhibiors and the antigen-specific TCR-transdeuced T cell transfusion would be expected in the future.
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| Academic Significance and Societal Importance of the Research Achievements |
現在使用されている分子標的薬や免疫チェックポイント阻害薬は多くのがんで有効である一方、生物学的製剤であるため薬価が高く国庫を圧迫することが大きな問題になっている。しかし、本研究で免疫増強作用を見出したプロテアソーム阻害薬は低分子化合物であり、医療経済的にも測り知れない有用性がある。また、本研究で樹立したTCR遺伝子導入T細胞が認識する抗原は、骨髄腫のみならず、膵臓がんなど複数の難治がんに高発現している。以上より、本研究の結果より提案されるプロテアソーム阻害薬と遺伝子改変T細胞療法の併用療法により複数の難治がんで治療効果が得られる可能性がある。
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Report
(4 results)
Research Products
(4 results)
