Development of novel T cell rejuvenation approach utilizing partial reprogramming

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K07651
• 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: Chiba University
• Principal Investigator: Yasuo Ouchi 千葉大学, 大学院医学研究院, 特任助教 (70553858)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: がん免疫療法 / 部分的初期化 / T細胞

Outline of Final Research Achievements

In recent years, cancer immunotherapy has been recognized as the "fourth therapy." However, its effectiveness is limited due to T cell exhaustion. This study aimed to develop a novel T cell rejuvenation technique for cancer immunotherapy by transiently expressing Yamanaka 4 factors and inducing partial reprogramming to alleviate T cell exhaustion. The findings demonstrated that partial reprogramming led to T cell proliferation, reduced exhaustion markers, and increased anti-tumor activity in mice. Similar effects were observed in human T cells, suggesting that partial T cell initialization with Yamanaka 4 factors could rejuvenate T cells.

Free Research Field

免疫学、幹細胞生物学、加齢医学

Academic Significance and Societal Importance of the Research Achievements

本研究成果はこれまで不可逆的な細胞変化であると考えられてきたT細胞の疲弊、老化は山中４因子の一過性発現による部分的初期化により若返りさせることができる可能性を示した研究成果である。この発見は近年「第四の治療法」として注目されているがん免疫療法において、がん患者、高齢者において疲弊しているT細胞を若返らせる技術として応用できる可能性がある。