Metabolic Reprogramming Requires Stem Cell Memory T Cell phenotypes for Cancer Immunotherapy
| Project/Area Number |
18K15290
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 50020:Tumor diagnostics and therapeutics-related
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| Research Institution | Keio University |
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Principal Investigator |
KONDO TAISUKE 慶應義塾大学, 医学部(信濃町), 助教 (60803765)
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| Project Period (FY) |
2018-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2018: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | がん免疫 / 代謝 / 免疫記憶 / ミトコンドリア / CAR-T療法 / がん免疫療法 / 免疫代謝 / 白血病 / 腫瘍免疫 / 細胞移入療法 / 腫瘍免疫学 / 代謝制御 |
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| Outline of Final Research Achievements |
Stem cell memory T (TSCM) cells are well-known as one of less differentiated-memory T cell population. We previously established a method for the induction of TSCM-like cells in vitro. With the support of the grant, we applied the established method for chimeric antigen receptor engineered-T (CAR-T) cell therapy and succeeded to convert normal CAR-T cells into TSCM-like CAR-T cells. The TSCM-like CAR-T cells showed potent anti-tumor activity in humanized leukemia model. We also found that the enhanced anti-tumor activity was dependent on mitochondrial biogenesis. The study has already been published on Cancer Research journal on 2020.
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| Academic Significance and Societal Importance of the Research Achievements |
キメラ型抗原受容体発現T(CAR-T)細胞移入療法はチェックポイント阻害剤と並ぶ、新たながん免疫療法である。米国ではすでに製剤として認可されており、小児および若年白血病患者に対して、高い治療成績を示している。しかしながら、長期間の寛解維持が困難であり、その原因の一つとして移入する細胞の品質が問題となっていた。本研究は従来のCAR-T細胞をより長期間体内で維持される様に改善する方法であり、新しいがん治療法として期待される。
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Report
(3 results)
Research Products
(5 results)
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[Journal Article] The NOTCH-FOXM1 Axis Plays a Key Role in Mitochondrial Biogenesis in the Induction of Human Stem Cell Memory-like CAR-T Cells.2020
Author(s)
Kondo T, Ando M, Nagai N, Tomisato W, Srirat T, Liu B, Mise-Omata S, Ikeda M, Chikuma S, Nishimasu H, Nureki O, Ohmura M, Hayakawa N, Hishiki T, Uchibori R, Ozawa K, Yoshimura A
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Journal Title
Cancer Res
Volume: 80
Issue: 3
Pages: 471-483
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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