Evaluation of immunological function of hTERT-specific transgenic T-cell receptor T cells for cancer immunotherapy

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K22804
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0901:Oncology and related fields
• Research Institution: Kanazawa University
• Principal Investigator: Kiichiro Kaji 金沢大学, 医学系, 協力研究員 (70886407)
• Project Period (FY): 2020-09-11 – 2022-03-31
• Keywords: 遺伝子改変T細胞 / hTERT / 免疫療法 / T細胞レセプター

Outline of Final Research Achievements

In recent years, liver cancer is still the fifth leading cause of cancer death in Japan. The high recurrence rate of hepatocellular carcinoma (the most common type of primary liver cancer) is a crucial problem. Cancer immunotherapy is an attractive method to solve the problem, therefore, we focused on one of the gene-modified T cell therapy, T cell receptor (TCR) gene-transduced T (TCR-T) cells. We generated human telomerase reverse transcriptase (hTERT)-specific TCR-T cells. A cytotoxicity assay showed antigen-specific cytotoxicity of hTERT-specific TCR-T cells.

Free Research Field

消化器病学

Academic Significance and Societal Importance of the Research Achievements

抗原特異的なTCR-Tの細胞傷害活性を示した本結果は，今後のTCR-T療法の基礎となる結果である．我々はすでに複数種類のhTERT特異的TCR遺伝子を同定し取得しており，今回の手法によって，より高い細胞傷害活性を示すTCR（Elite TCR）の選定を行うことができ，より効果的なTCR-T療法を目指すことが可能である．さらに今後，実際にヒトを対象とした臨床試験への応用を視野に免疫不全マウスへ肝癌細胞株を生着させた肝細胞癌治療動物モデルによるTCR-T療法の安全性と抗腫瘍効果を評価していく．そしてこの結果をもとにヒト臨床試験の施行を目指している．