Establishment of CAR-T cell therapy utilizing precursor T cell

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K16277
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 54010:Hematology and medical oncology-related
• Research Institution: Tokyo University of Science
• Principal Investigator: Shigehiro Tsukasa 東京理科大学, 研究推進機構生命医科学研究所, 助教 (30876058)
• Project Period (FY): 2021-04-01 – 2023-03-31
• Keywords: T細胞免疫療法 / キメラ抗原受容体 / T細胞受容体 / T前駆細胞

Outline of Final Research Achievements

Genetically engineered T cells using cancer-reactive receptor have made great strides in cancer therapy. However, the engineered T cells generated from T cells in peripheral blood are often exhausted. Although hematopoietic stem/progenitor cells (HSPCs) have been proposed to generate "young" engineered T cells, the number of the T cells from HSPCs are highly limited. In this study, progenitor T cells that have self-renewal capacity were applied to generate a large number of stem-derived engineered T cells. Cancer-reactive receptor engineered progenitor T cells were successfully established and greatly expanded ex vivo. The progenitor T cells were efficiently differentiated into CD8+ T cells that had antigen-specific anticancer activity. Therefore, progenitor T cells are a promising source of the engineered T cells for cancer immunotherapy.

Free Research Field

がん免疫学

Academic Significance and Societal Importance of the Research Achievements

本研究では、T前駆細胞の自己複製能を利用することによって、遺伝子改変T細胞を大量に作製する技術を開発することに成功した。これまで、造血幹前駆細胞から遺伝子改変T細胞を作製する方法が考案されているが、その増幅は難しく、得られる遺伝子改変Τ細胞の数は大きく制限されていた。本研究で作製した遺伝子改変T前駆細胞は容易に増幅することができ、また、効率的に成熟T細胞へと分化させることが可能である。従って、安価に大量の遺伝子改変Τ細胞を作製できることが期待されるため、がん免疫治療薬として社会に大きく還元できると考えられる。