Development of a novel method for T-cell preparations targeting cancer using genome editing in human and monkey induced pluripotent stem cells

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K07712
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 50020:Tumor diagnostics and therapeutics-related
• Research Institution: Shiga University of Medical Science
• Principal Investigator: TERADA Koji 滋賀医科大学, 医学部, 准教授 (70342722)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: T細胞受容体 / T細胞 / がん / カニクイザル

Outline of Final Research Achievements

To develop effective adoptive cell transfer therapy using T cell receptor (TCR)-engineered T cells, it is critical to isolate tumor-reactive TCRs that have potent anti-tumor activity. Characterization of tumor reactivity of tumor-infiltrating lymphocytes (TILs) from non-human primate tumors could improve anti-tumor activity of TCR-engineered T cells in preclinical research. In this study, we isolated TCR genes from TILs in a cynomolgus macaque model of tumor transplantation in which the tumors were infiltrated with CD8+ T cells and were eventually rejected. We identified multiple TCR pairs with high frequency. We showed that the recurrent TCRs exhibited cytotoxic activity to tumor cells in vitro and potent anti-tumor activity in mice transplanted with tumor cells. These results imply that this tumor transplantation macaque model recapitulates key features of human TILs and can serve as a platform toward pre- clinical studies of non-human primate tumor models.

Free Research Field

がん免疫

Academic Significance and Societal Importance of the Research Achievements

本研究では、カニクイザルの腫瘍から得られた腫瘍浸潤リンパ球（TIL）の細胞表面発現分子とT細胞受容体遺伝子を解析した。その結果、カニクイザルのTILはヒトのTILと共通の性質を有すること、外来性にTCRを発現させたT細胞を用いたがん免疫療法の前臨床研究においてカニクイザルが有用な動物モデルとなる可能性があることなどが示唆された。