Development of a chimeric synthetic receptor to suppress T cell exhaustion for use in adoptive cancer immunotherapy

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K22552
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 50:Oncology and related fields
• Research Institution: Aichi 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, 分野長 (70706960)
• Project Period (FY): 2019-06-28 – 2021-03-31
• Keywords: 養子免疫療法 / キメラ抗原受容体 / T細胞疲弊 / サイトカイン / メモリーT細胞

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 into a patient. To suppress T cell exhaustion and provide long-lived potential in antitumor T cells, we developed an artificial receptor that blocks PD1 signaling as well as activates cytokine signaling. The artificial receptor-expressing chimeric antigen receptor (CAR)-engineered T cells showed increased STAT5 phosphorylation and accomplished superior proliferation upon antigen stimulation. Moreover, the artificial receptor-transduced CAR-T cells produced more cytokines when cultured with PDL1-positive tumor cells. These results demonstrate that the newly developed receptor provides T cells with resistance to exhaustion and long-surviving capacity.

Free Research Field

免疫学

Academic Significance and Societal Importance of the Research Achievements

がん細胞を特異的に攻撃するT細胞を体外で準備して患者に輸注する養子免疫療法は、近年一部の血液がんで優れた効果が実証されたCAR-T細胞療法に代表されるように、難治性がんに対する有望な治療法であるが、多くのがんに対しては未だ治療効果が証明されていない。本研究開発の知見によりT細胞機能を高めることで、養子免疫療法の治療効果、適応がん疾患を拡大させられる可能性がある。