Generation of tumor-reactive T cells from iPS cell-derived NKT cells and application for pancreatic cancer therapy

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K10717
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: National Cancer Center Japan
• Principal Investigator: Uemura Yasushi 国立研究開発法人国立がん研究センター, 先端医療開発センター, ユニット長 (40364781)
• Co-Investigator(Kenkyū-buntansha): 福田 恭子 (張エイ) 国立研究開発法人国立がん研究センター, 先端医療開発センター, 研究員 (00643719)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 外科 / がん / 免疫 / 再生医療 / 人工多能性幹細胞

Outline of Final Research Achievements

The re-iNKT cells by themselves showed the NK cell-like cytotoxicity against all of the tested cancer cell lines, which was mediated by NKG2D and DNAM-1. They inhibited the growth of K562 chronic myelogenous leukemia in a xenografted mouse model and prolonged the mouse survival. We generated the re-iNKT cells expressing a glypican-3 (GPC3)-reactive chimeric antigen receptor (CAR). The GPC3-CAR-transduced re-iNKT cells revealed a cytotoxicity against a GPC3-expressing SK-Hep1 cancer cell line. However, the strength of the cytotoxicity was equal to that of wild-type re-iNKT cells. To clarify the function of GPC3-CAR, we used peripheral blood-derived T cells for GPC3-CAR gene transfer. The GPC3-CAR-transduced T cells revealed the enhanced cytotoxicity against the GPC3-expressing JHH7 cell line compared to the wild-type T cells, indicating that the CAR construct is intact. re-iNKT cells can be a cell platform potentially utilized for cancer immunotherapy.

Free Research Field

がん免疫療法

Academic Significance and Societal Importance of the Research Achievements

iNKT細胞は、アロ拒絶反応を惹起しないT細胞受容体を持つ為、iPSCから再生したiNKT細胞は、がん治療を目的とした他家投与用のエフェクター細胞プラットフォームとして有望である。再生iNKT細胞が抗腫瘍効果を示す「がん細胞」の情報は、学術的、及び 臨床的に重要である。