• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to project page

2022 Fiscal Year Final Research Report

Generation of long-surviving antitumor T cells by genetic modification for optimal adoptive immunotherapy

Research Project

  • PDF
Project/Area Number 20H03543
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 50020:Tumor diagnostics and therapeutics-related
Research InstitutionAichi Cancer Center Research Institute

Principal Investigator

Kagoya Yuki  愛知県がんセンター(研究所), 腫瘍免疫応答研究分野, 客員研究員 (70706960)

Project Period (FY) 2020-04-01 – 2023-03-31
Keywords養子免疫療法 / 悪性腫瘍 / メモリーT細胞 / キメラ抗原受容体 / エピジェネティック因子 / 転写制御因子 / T細胞疲弊
Outline of Final Research Achievements

The overarching goal of this study is to enhance therapeutic efficacy of adoptive cancer immunotherapy, in which tumor antigen-specific T cells are prepared in vitro and infused back into the patient. We aimed to improve long-surviving capacity of antitumor T cells through genetic engineering. We further addressed molecular mechanisms of how modification of the identified target(s) affects T cell longevity.
We identified multiple targets associated with self-renewal proliferation of T cells. Especially, genetic ablation of the transcription factor PRDM1, which encodes Blimp1, significantly improved persistence of antitumor T cells. We confirmed that Blimp1-deficient T cells can induce durable antitumor response using multiple mouse tumor models. In addition to these findings, we analyzed molecular profiles of exhausted T cells in detail and identified that the expression of CD83 marks precursor exhausted T cells, which will be useful to finely dissect dysfunctional T cells.

Free Research Field

免疫学

Academic Significance and Societal Importance of the Research Achievements

本研究成果は、がんに対する養子免疫療法、例えば現在血液腫瘍に対して実臨床で用いられているキメラ抗原受容体 (CAR)導入T細胞療法などの治療効果を高めることへの応用性を持つ。CAR-T細胞は一過性には治療効果が高いが、その後の再発などで持続的な治療効果が得られる症例は限定的であることから、輸注されたT細胞の長期生存能を高めることで、治癒を目指した治療法開発が可能となる。また免疫チェックポイント阻害剤をはじめとするがん免疫療法では、治療効果を予測するバイオマーカー探索が重要であり、長期生存能に優れた前駆疲弊分画をマークするCD83分子に関する知見は有効性予測に寄与する可能性がある。

URL: 

Published: 2024-01-30  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi