Immunotherapy of HBV-related advanced hepatocellular carcinoma with short-term HBV-specific TCR expressed T cells: results of dose escalation, phase I trial
Fanping Meng, Jinfang Zhao, Anthony Tanoto Tan, Wei Hu, Si-Yu Wang, Jiehua Jin, Juan Wu, Yuanyuan Li, Lei Shi, Jun-Liang Fu, Shuangjie Yu, Yingjuan Shen, Limin Liu, Junqing Luan, Ming Shi, Yunbo Xie, Chun-Bao Zhou, Regina Wanju Wong, Wai Lu-En, Sarene Koh, Antonio Bertoletti, Tingting Wang, Ji-Yuan Zhang & Fu-Sheng Wang
Hepatology International volume 15, pages 1402–1412 (2021)Cite this article
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Abstract
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
Adverse events were observed in two participants among the 8 patients enrolled. Only one patient experienced a Grade 3 liver-related adverse event after receiving a dose of 1 × 105 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 of clinical efficacy support the continued development and eventual application of this treatment strategy in patients with advanced HBV-related HCC.
Clinical trials registration
This study was registered at ClinicalTrials.gov (NCT03899415).作者: StephenW 时间: 2021-12-8 20:09