Development of Novel CAR-T cell with NK cell-like specificity against refractory cancer

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K08317
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 52050:Embryonic medicine and pediatrics-related
• Research Institution: Niigata University
• Principal Investigator: Imai Chihaya 新潟大学, 医歯学系, 准教授 (90419284)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: キメラ抗原受容体 / CAR-T細胞 / 難治がん / NK細胞 / NK細胞受容体 / NKp44 / NKG2D / NKp30

Outline of Final Research Achievements

To develop a novel genetically modified human T-cell therapy that is able to safely target multiple types of refractory cancers, we have conducted i) detailed comparative functional analysis of T cells transduced with various NKp44-based CARs and investigation for potential ligands of NKp44, ii) development of other CAR genes for dual targeting strategy, iii) creation of novel CARs with inhibitory functions to prevent unexpected injuries on normal tissues. Further studies are needed to make CAR-T cell therapy applicable to a wider range of cancer types.

Free Research Field

がん免疫治療

Academic Significance and Societal Importance of the Research Achievements

新規開発のNKp44改変キメラ抗原受容体（CAR）遺伝子を導入したT細胞機能の詳細を明らかにし、現状で最良の第2世代CAR遺伝子を決定した。このCAR-T細胞は、白血病、リンパ腫だけでなく、様々な小児・思春期の固形腫瘍細胞を認識した。一方、NKp44の複数の候補リガンドを詳細に検討したが、いずれの候補分子も細胞表面への強制発現による細胞傷害活性誘導を生じなかった。最後に、抑制機能を持つCARを作成し機能を確認したが、正常組織にあり腫瘍にない抗原（リガンド）を探索する必要があり、さらなる検討を要する。