Biomarker-based manufacture of MAGE-A4/CAR-T cell in immunotherapy for esophageal cancer

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K08682
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 55020:Digestive surgery-related
• 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)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 食道癌

Outline of Final Research Achievements

In this study, to develop a CAR-T therapy targeting the MAGE-A4 antigen, which is expressed in approximately 50% of esophageal cancers, we comprehensively analyzed the trait analysis, gene expression, and metabolites of TCR transgenic T cells already infused in clinical trials, and biomarkers related to clinical trial information (adverse events, clinical efficacy) Cytokine release syndrome (CRS), clinical efficacy and immunocytological analysis of manufactured TCR-T cells and post-infusion peripheral blood TCR-T cells were performed using clinical specimens in which NY-ESO-1/TCR-T cell infusion was performed and stored under consent.
Heterogeneous T cell marker expression of manufactured TCR-T cells was observed in the analysis of T cell products of post-infusion specimens and their peripheral blood samples.

Free Research Field

腫瘍免疫学

Academic Significance and Societal Importance of the Research Achievements

CAR-T細胞療法が急性白血病、悪性リンパ腫、多発性骨髄腫で実用化されて、治療効果を発揮しているが、固形腫瘍（癌、肉腫）に対するT細胞療法は未だ実用化されていない。本研究は難治性固形腫瘍である再発・転移食道癌に対するCAR-T細胞療法への実用化を目指す基盤研究であり、製造するT細胞の適切化が可能となる研究成果であり、臨床試験の計画が明確となった。
標的抗原であるMAGE-A4の腫瘍組織での検出法が確立され、治療対象の適切化がなされた。
本研究の成果を踏まえて、実用化を目指す治験の実施が開始された。