Immunotherapy of HBV-related advanced hepatocellular carcinoma with short-term HBV-specific TCR expressed T cells: results of dose escalation, phase I trial

作者：Fanping Meng, Jinfang Zhao, Anthony T. Tan, Wei Hu, Siyu Wang, Jiehua Jin, Juan Wu, Yuanyuan Li, Lei Shi, Junliang Fu, Shuang-jie Yu, Yingjuan Shen, Limin Liu, Junqing Luan, Ming Shi, Yunbo Xie, Chun‐Bao Zhou, Regina Wanju Wong, Lu‐En Wai, Sarene Koh, Antonio Bertoletti, Tingting Wang, Jiyuan Zhang, Fu‐Sheng Wang · 发表于：Hepatology International · 年份：2021 · DOI：10.1007/s12072-021-10250-2 · 被引用次数：110 · 研究领域：Hepatitis B Virus Studies、CAR-T cell therapy research、Cancer Immunotherapy and Biomarkers

BACKGROUND & AIMS: Immunotherapy with hepatitis B virus (HBV)-specific TCR redirected T (HBV-TCR-T) cells in HBV-related hepatocellular carcinoma (HBV-HCC) patients after liver transplantation was reported to be safe and had potential therapeutic efficacy. We aim to investigate the safety of HBV-TCR-T-cell immunotherapy in advanced HBV-HCC patients who had not met the criteria for liver transplantation. METHODS: We enrolled eight patients with advanced HBV-HCC and adoptively transferred short-lived autologous T cells expressing HBV-specific TCR to perform an open-label, phase 1 dose-escalation study (NCT03899415). The primary endpoint was to evaluate the safety of HBV-TCR-T-cell therapy according to National Cancer Institute Common Terminology Criteria for Adverse Events (version 4.03) during the dose-escalation process. The secondary endpoint was to assess the efficacy of HBV-TCR-T-cell therapy by evaluating the anti-tumor responses using RECIST criteria (version 1.1) and the overall survival. RESULTS: HBV-TCR-T cells/kg, then normalized without interventions with immunosuppressive agents. Among the patients, one achieved a partial response lasting for 27.7 months. Importantly, most of the patients exhibited a reduction or stabilization of circulating HBsAg and HBV DNA levels after HBV-TCR-T-cell infusion, indicating the on-target effects. CONCLUSIONS: The adoptive transfer of HBV-TCR-T cells into advanced HBV-HCC patients were generally safe and well-tolerated. Observations...