T cell optimization for effective CAR-T cell therapy to refractory esophageal cancer

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K22655
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 55:Surgery of the organs maintaining homeostasis and related fields
• Research Institution: Mie University
• Principal Investigator: Kageyama Shinichi 三重大学, 医学系研究科, リサーチアソシエイト (80194695)
• Co-Investigator(Kenkyū-buntansha): 宮原 慶裕 三重大学, 医学系研究科, 産学官連携講座教授 (10582083) ; 加藤 琢磨 三重大学, 医学系研究科, 准教授 (60224515)
• Project Period (FY): 2019-06-28 – 2022-03-31
• Keywords: 食道癌 / がん免疫療法 / T細胞治療

Outline of Final Research Achievements

To develop a CAR-T therapy for refractory esophageal cancer, we comprehensively analyzed the phenotype, immune function, and transcriptome (including gene expression analysis related to glucose and fat metabolism) of TCR-gene transduced T cells infused in clinical trials to identify factors associated with in vivo persistence and clinical efficacy.
Factors associated with in vivo persistence and clinical efficacy were explored, and subpopulations selected. The CRS (cytokine release syndrome) pathogenesis involved host-derived cytokines after TCR-T infusion and was significantly related to the differentiation traits of infused TCR-T (manufactured T cells). It was also inferred that TCR-T traits (CD39, CD244) and clinical response (CRS, tumor shrinkage) were involved after infusion.

Free Research Field

臨床腫瘍学

Academic Significance and Societal Importance of the Research Achievements

転移再発食道癌に対する有効な治療手段がないのが現状であるが、近年免疫療法への期待が高い。本研究はT細胞療法の基盤研究であり、新しいCAR-T細胞療法の臨床開発のための基盤研究である。CAR-T細胞療法ではサイトカイン放出症候群を避けながら有効性を向上させることが重要であり、本研究では臨床反応に関連する因子が特定された。