Optimization of chimeric antigen receptor T cells (CAR-T) targeting GM-CSF receptor for the treatment of pediatric leukemia

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K10103
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Shinshu University
• Principal Investigator: Nakano Shigeru 信州大学, 医学部附属病院, 特任研究員 (30791313)
• Co-Investigator(Kenkyū-buntansha): 中沢 洋三 信州大学, 学術研究院医学系, 教授 (60397312)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: キメラ抗原受容体T細胞 / GM-CSF / リガンド / 骨髄性白血病

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.

Free Research Field

小児血液学

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。