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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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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