| Project/Area Number |
18K08988
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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 56010:Neurosurgery-related
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| Research Institution | University of Tsukuba |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
石川 栄一 筑波大学, 医学医療系, 准教授 (30510169)
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| Project Period (FY) |
2018-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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 | 不活化ウイルス粒子 / グリオーマ / 制御性T細胞 / 免疫チェックポイント / PD-L1 / 多角的免疫療法 / glioma |
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| Outline of Final Research Achievements |
Hemagglutinating virus of Japan envelope (HVJ-E) is a replication-defective inactivated virus particle made from Sendai virus (HVJ) by treating with ultraviolet irradiation to destroy the viral genome RNA. HVJ-E enhances anti-tumor immunity through activation of effector T cells and natural killer cells and inhibition of regulatory T cells (Treg), although it was originally developed as a versatile drug delivery system. In the present study, we incorporated siRNA targeting PD-L1 into HVJ-E to suppress tumor PD-L1 expression and demonstrated significant antitumoral effects in mouse brain glioma models due to synergistic activation of anti-tumor immunity. We developed a novel immunotherapeutic approach against glioma to combine the immune-activating and Treg suppressive features of HVJ-E itself with siRNA-mediated PD-L1 inhibition.
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| Academic Significance and Societal Importance of the Research Achievements |
グリオーマに対する免疫療法研究において、腫瘍局所での免疫逃避機構の制御が重要であることが明らかとなり、特にPD-1/PD-L1経路などの免疫逃避機構を標的とした治療法に関する研究がさかんに行われている。本研究は、PD-1/PD-L1経路のみならず制御性T細胞をも標的とし、腫瘍局所で免疫逃避機構を多角的に解除するというこれまでにない新たなアプローチであり、革新的な免疫療法といえる。不治の病であるグリオーマに対して、このような新規性の高い治療法の開発は、グリオーマ治療のブレークスルーとなりうることから社会的意義は大きいと考えられる。
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