Investigation of antigen-specific T cell receptors for the treatment of hepatocellular carcinoma

2021 Fiscal Year Final Research Report

• Project/Area Number: 18K15778
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: Kanazawa University
• Principal Investigator: Tamai Toshikatsu 金沢大学, 医学系, 助教 (40782082)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Keywords: T細胞受容体 / 肝細胞癌

Outline of Final Research Achievements

Basic data on T cell receptors (TCRs) recognizing hepatocellular carcinoma-associated antigens obtained from hepatocellular carcinoma patients. The TCR of cytotoxic T cells (CTLs) specific for AFP, MRP3, and hTERT-derived antigens, which are hepatocarcinoma-associated antigens, were incorporated into siRNA vectors that suppress expression of the endogenous TCR. The cytotoxic activity of those TCRs against hepatocellular carcinoma cell lines was visually confirmed by time-lapse observation using a confocal laser microscope system.

Free Research Field

消化器内科

Academic Significance and Societal Importance of the Research Achievements

TCR治療を臨床応用するためには、内在性TCRと導入TCRとのミスペアリングを抑制しながら、治療効果の高いTCRを取得する必要がある。本研究においては、新規の肝がん関連抗原由来特異的TCRを取得することはできなかったが、既存のTCRを用いて、内在性TCR発現を抑制するベクターに組み込んだ場合の細胞傷害活性を確認した。本研究結果および用いた手法は、肝がんに対する免疫療法を確立するために有用な情報になると考えられる。