Generation and analysis of exhausted CAR-T cell : For developing un-exhausted CAR-T cell
| Project/Area Number |
18K07272
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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 | Dokkyo Medical University |
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Principal Investigator |
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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 |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | CAR-T細胞 / 疲弊 / 免疫チェックポイント / 共刺激シグナル / 転写因子 / HIV / 免疫療法 |
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| Outline of Final Research Achievements |
In this study, we found that CAR-T cell with a CD28-derived co-stimulatory signal domain (CSSD) exhibited exhausted phenotype whereas the one with a herpes virus entry mediator-derived CSSD exhibited exhaustion-resistant phenotype. We also found that early exhaustion status of the CAR-T cell could affect responsiveness of the CAR-T cells. Phenotypic analysis of the CAR-T cells also showed that early CAR-T cell exhaustion is associated with CAR-mediated tonic signaling due to CAR clustering. In addition, we explored the factors for avoiding CAR-T cell exhaustion using CD28-CAR-T cell as a model system of exhausted CAR-T cell.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究の成果は、進行期造血器腫瘍で高い奏効率を示しているCAR-T細胞療法を、固形腫瘍に応用するための基盤となる成果である。疲弊CAR-T細胞の性状解析と疲弊CAR-T細胞を用いたスクリーニングから、CAR-T細胞の疲弊回避の可能性が示唆された。これは、固形腫瘍で見られるCAR-T細胞の疲弊化による不応答性を改善に役立てられると考えられる。
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Report
(5 results)
Research Products
(6 results)
