Development of iPS cell-derived T cells with novel factors that dramatically improve anti-tumor efficacy against solid tumor

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K20821
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0901:Oncology and related fields
• Research Institution: Kyoto University
• Principal Investigator: Ishikawa Akihiro 京都大学, iPS細胞研究所, 特定研究員 (30966049)
• Project Period (FY): 2022-08-31 – 2024-03-31
• Keywords: iPS細胞 / iPS細胞由来T細胞 / 遺伝子改変T細胞療法 / 固形腫瘍 / 腫瘍免疫

Outline of Final Research Achievements

iPS cell-derived T (iPS-T) cells infiltrated in solid tumors were analyzed and where useful genes were extracted from the cell populations that were considered functional. As a result, we succeeded in finding several candidate genes that could improve the anti-tumor efficacy against solid tumors. Candidate genes were expressed in iPS-T cells and found that we succeeded in further sorting out the genes that significantly improved the functionality of the iPS-T cells compared to conventional iPS-T cells. In an analysis using a mouse model of solid tumors, progression of solid tumors was significantly suppressed in the group of mice treated with sorted gene-expressing iPS-T cells, suggesting that the sorted genes are very important for the functionality of iPS-T cells.

Free Research Field

がん免疫分野

Academic Significance and Societal Importance of the Research Achievements

本研究で選別に成功した遺伝子はこれまでT細胞の機能向上に貢献するよりはT細胞・幹細胞分化に関係していることが多く報告されていた。実際に選別遺伝子を発現したiPS-T細胞はT細胞の抗腫瘍効果が高い集団を保持した細胞であった。選別遺伝子がiPS細胞からのT細胞分化に重大な影響を与える可能性を鑑みて、今後、選別遺伝子をiPS細胞に導入してT細胞分化を行う予定である。本研究によってこれまでにない機能的iPS-T細胞の作製や、T細胞分化における新しい知見を見出すといった基礎科学的視点での研究の発展が期待される。