| Project/Area Number |
18K08309
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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 53050:Dermatology-related
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| Research Institution | Kyoto University (2019-2020)
Keio University (2018) |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
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: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 悪性黒色腫 / beta-catenin / がん免疫療法 / β-カテニン / メラノーマ |
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| Outline of Final Research Achievements |
Although anti PD-1 Ab showed significant anti-tumor effects in melanoma patients, there are still a lot of non-responders. It is important to develop new combined therapies and to identify biomarkers. We previously reported that activated beta-catenin pathways in melanoma cells induced immune suppression through ectopic production of immunosuppressive molecules. In this study, we showed a drug targeting fatty acid metabolism could enhance anti-tumor immune responses such as anti PD-1 Ab therapeutic effects through targeting beta-catenin pathways in cancer cells, which resulted in enhancement of their chemokine production. We also found this drug directly activated T cell and dendritic cell functions. These results suggest that this drug can be used in combined therapies with anti PD-1 Ab through targeting both cancer cells and immune cells.
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| Academic Significance and Societal Importance of the Research Achievements |
悪性黒色腫において、抗PD-1抗体などの免疫チェックポイント阻害薬は、優れた臨床効果を示したが、単独使用では不十分で、併用療法の開発とバイオマーカーの探索が必要である。本研究では、脂質代謝を標的とした阻害薬を用いて、抗ＰＤ－１抗体の治療効果を増強できることを示した。このような作用はこれまでに報告がなく、学術的に新規のものである。また、本分子を標的とした治療薬は、既に高脂血症などの脂質代謝疾患の治療薬として、臨床試験が行われ安全性が確認されている物も多い。そのため、抗PD-1抗体との併用療法の開発もより早く実施できる可能性があり、臨床的、社会的にも価値がある。
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