Development of a Novel CAR-T Cell Therapy for Pediatric Malignancies Using KIR Receptors With Genetic Modification

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K15878
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 52050:Embryonic medicine and pediatrics-related
• Research Institution: Niigata University
• Principal Investigator: Yasushi Kasahara 新潟大学, 医歯学総合研究科, 客員研究員 (40866480)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: キメラ抗原受容体 / NK細胞 / 白血病 / 固形腫瘍 / 免疫療法

Outline of Final Research Achievements

Novel chimeric antigen receptors (CAR) were developed in this study. Multiple CAR constructs were created, and the optimal CAR structure was determined by comparing CAR-T cell properties such as CAR expression levels and target cytotoxicity when introduced into human T cells. In parallel, we comprehensively analyzed the expression of ligands on the cell surface of various tumor cell lines and investigated the induction of ligands. We then examined the cytotoxicity of CAR-T cells against various tumor cell lines. Further research is needed to realize novel CAR-T cell therapies.

Free Research Field

免疫細胞療法

Academic Significance and Societal Importance of the Research Achievements

難治性の急性リンパ性白血病およびリンパ腫、多発性骨髄腫に対するキメラ抗原受容体（CAR）遺伝子導入T細胞（CAR-T）療法の有効性は広く知られ、本邦では臨床現場で広く用いられている。一方で急性骨髄性白血病や固形腫瘍への応用が期待されているが、いまだ実現していない。本研究では、NK細胞が有する腫瘍細胞を認識する能力をT細胞に付与するCAR遺伝子を開発した。本研究で作成したCARは、B細胞性の血液腫瘍以外を標的とするCAR-T療法の候補となり得る。