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2022 Fiscal Year Final Research Report

Development of immunotherapy using iPS-NKT cells for glioblastoma

Research Project

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Project/Area Number 20K17917
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 56010:Neurosurgery-related
Research InstitutionChiba University

Principal Investigator

Kobayashi Masayoshi  千葉大学, 医学部附属病院, 助教 (10867857)

Project Period (FY) 2020-04-01 – 2023-03-31
Keywords膠芽腫 / NKT細胞 / iPS-NKT / 抑制性免疫 / 養子免疫療法
Outline of Final Research Achievements

In this study, we analyzed immune cells in the peripheral blood of glioma patients and analyzed tumor-infiltrating immune cells using resected tumors. Among peripheral blood mononuclear cells from glioblastoma (GBM) patients, suppressive immune cell population were increased, and and T cells were decreased, while Natural Killer T (NKT) cells were unaffected. Moreover, tumor-infiltrating lymphocytes from GBM patients included exhausted T cells, but few NKT cells. Intracranial administration of NKT cells extended survival and inhibited tumor growth in the orthotopic GBM mouse model in the presence of T cells.

Free Research Field

脳神経外科学

Academic Significance and Societal Importance of the Research Achievements

膠芽腫は、標準的治療でも生存期間の中央値は約15か月と非常に予後が悪く、新規治療法の開発が喫緊の課題である。本研究で膠芽腫患者は免疫抑制状態にあるが末梢血のNKT細胞数は保たれており、腫瘍微小環境で疲弊しているT細胞は確認されたがNKT細胞は認めなかった。このことから、NKT細胞の細胞傷害活性を期待し、膠芽腫マウスモデルに対し、NKT細胞を用いた養子免疫細胞療法を行ったところ、T細胞の存在下で抗腫瘍効果が認められた。この研究結果は、実臨床を目指すためにNKT細胞の質と供給量を確保するための供給源となりうるiPS細胞由来NKT細胞 (iPS-NKT) を用いた養子免疫療法の足掛かりとなる。

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Published: 2024-01-30  

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