| Project/Area Number |
18K07268
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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 | Yamaguchi University |
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Principal Investigator |
ADACHI Keishi 山口大学, 大学院医学系研究科, 講師 (40598611)
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| Co-Investigator(Kenkyū-buntansha) |
玉田 耕治 山口大学, 大学院医学系研究科, 教授 (00615841)
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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 |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 抗核抗体 / CAR-T細胞 / 概念実証実験 / がん / CAR / キメラ抗原受容体 / T細胞 / 細胞内シグナル |
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| Outline of Final Research Achievements |
The goal of this project is to generate a novel cancer therapy using the next generation chimeric antigen receptor (CAR)-expressing T cell that exerts anti-cancer effects more effectively than the conventional one. So far, the following results have been obtained;
1) The construct for the next generation CAR-T cell with which a CAR specific to a tumor antigen and an artificial protein consisting of an inhibitory molecule against an intracellular signaling molecule and a single-chain Fv of antinuclear antibody, designated “L scFv”, linked by a linker could be concomitantly expressed was designed. 2) The next generation CAR-T cells simultaneously expressed the CAR and the artificial proteins as intended. 3) The expression of a nucleic acid transporter which is required for transmembrane translocation of the antinuclear antibodies was confirmed on several murine cancer cell lines with flow cytometry.
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| Academic Significance and Societal Importance of the Research Achievements |
CAR-T細胞療法の臨床試験は欧米や中国を中心に進行しており、米国では2017年8月に、我が国では2019年3月に、血液悪性腫瘍を対象として承認を受けた。しかし我が国は、臨床試験の件数で欧米や中国に大きく水をあけられている。現在のCAR-T細胞療法が抱える『固形がんに対して有効性が乏しいこと』などの問題点を克服することで、現状を打破してグローバルスタンダードとなりうる我が国発の次世代型CAR-T細胞療法を開発することは喫緊の課題である。今回、がん組織内に形成される免疫抑制環境を克服するこれまでにない手段として、抗核抗体の細胞膜透過能を利用した細胞内分子の制御を考えつき、本研究課題を申請した。
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