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

• 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
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: T細胞受容体 / 肝細胞癌 / ペプチド / 肝癌関連抗原 / 肝癌 / 免疫

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.

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。

Research Products

• [Journal Article] A novel α-fetoprotein-derived helper T-lymphocyte epitope with strong immunogenicity in patients with hepatocellular carcinoma (2020)
  • Author(s): Tamai Toshikatsu、Mizukoshi Eishiro、Kumagai Masashi、Terashima Takeshi、Iida Noriho、Kitahara Masaaki、Shimakami Tetsuro、Kitamura Kazuya、Arai Kuniaki、Yamashita Taro、Sakai Yoshio、Yamashita Tatsuya、Honda Masao、Fushimi Kazumi、Kaneko Shuichi
  • Journal Title: Scientific Reports Volume: 10 Issue: 1 Pages: 4021-4021
  • DOI: 10.1038/s41598-020-60843-4
  • Peer Reviewed / Open Access
• [Presentation] Identification of a novel α-protein-derived helper T cell epitope in hepatocellular carcinoma patients. (2019)
  • Author(s): Toshikatsu Tamai, Eishiro mizukoshi, Shuichi Kaneko.
  • Organizer: AASLD The liver meeting 2019
  • Int'l Joint Research