| Project/Area Number |
17K10103
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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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| Research Field |
Pediatrics
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| Research Institution | Shinshu University |
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Principal Investigator |
Nakano Shigeru 信州大学, 医学部附属病院, 特任研究員 (30791313)
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| Co-Investigator(Kenkyū-buntansha) |
中沢 洋三 信州大学, 学術研究院医学系, 教授 (60397312)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | キメラ抗原受容体T細胞 / GM-CSF / リガンド / 骨髄性白血病 / CAR-T / キメラ抗原受容体 / 若年性骨髄単球性白血病 / 急性骨髄性白血病 |
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| Outline of Final Research Achievements |
We performed translational researches of our chimeric antigen receptor T cells (CAR-T) targeting GM-CSF receptor for the treatment of pediatric leukemia in this grant. We have previously developed 1st generation GMR CAR-T cells. In 2017, we established the modified GMR CAR-T that has ability of GM-CSF knock-down by shRNA to reduce GM-CSF secretion from itself during killing of leukemia cells, and its anti-tumor activity was superior to 1st generation one. In 2018, we assessed the receptor selectivity of GMR CAR-T using our established GMRα or β stably-expressing K562 cells. In final year, we prepared the extracellular-domain protein of GMR CAR-T as part of safety study for clinical applications and tissue cross-reactivity study has been started. Based on our results, we are preparing to start a doctor-initiated clinical trial of GMR CAR-T.
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| Academic Significance and Societal Importance of the Research Achievements |
JMMLに対するCAR-T細胞療法はこれまで国内外で報告されていない。GMRを標的としたCAR-T細胞の前例もなく、JMMLおよびAMLに対する安全で有効性の高い新たな治療選択肢を提供できる。GMR CAR-T細胞の臨床開発の実現は、AML治療において大きな臨床的意義をもたらすと期待される。トランスポゾン遺伝子改変技術を用いたCAR-T細胞療法の開発は、研究分担者のグループで臨床応用に向けた準備が進められており、本邦における速やかな臨床試験への移行が期待できる。
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