| Project/Area Number |
16K10179
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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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| Research Field |
Dermatology
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| Research Institution | St. Marianna University School of Medicine |
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Principal Investigator |
Kadono Takafumi 聖マリアンナ医科大学, 医学部, 教授 (80292910)
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| Project Period (FY) |
2016-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 悪性黒色腫 / PD-1 / CTLA-4 / poly IC / 抗PD-1抗体 / イミキモド |
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| Outline of Final Research Achievements |
Although immunocheckpoint inhibitors have revealed unprecedented therapeutic effect for malignant melanoma, they are effective for only 30% of the patients. To synergistically enhance the effect of immunocheckpoint inhibitors, we added local immunotherapy against melanoma and examined its therapeutic effect. Melanoma cells were injected into the back of the mice. After the tumor was formed, immunocheckpoint inhibitors, such as anti-PD-1 antibodies and anti-CTLA-4 antibodies were intraperitoneally administered concomitant with local injection of allogeneic immunoglobulins and poly IC, an immuno-stimulator. This therapy significantly retarded the tumor growth, and this tumor growth inhibition was mediated by the increase of IL-6 and the decrease of IL-10.
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| Academic Significance and Societal Importance of the Research Achievements |
悪性黒色腫に対する治療として免疫チェックポイント阻害薬が用いられるが、全ての患者さんに効果を示すわけではなく、種々の併用療法が模索されている。今回の研究で、免疫チェックポイント阻害薬に加えて局所免疫療法として異種の免疫グロブリンと免疫賦活薬を加えることで、抗腫瘍効果が高まることが判った。今回の動物実験の結果を人に応用することで、より効果的な免疫チェックポイント阻害薬を活用した悪性黒色腫の治療に繋がる可能性が考えられる。
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