HBV-Specific TCR–T Cell Therapy Combining mRNA Electroporation and Lentiviral Transduction: Treatment Regimen for Recurrent HBV-Related HCC after Liver Transplantation

作者：Qiang Zhao, Jinbo Huang, Weixin Luo, Haidong Tan, Regina Wan Ju Wong, Zhiying Liu, Meiting Qin, Jiahao Li, Sarene Koh, Lu‐En Wai, Tingting Wang, Jia Dan, Zhiyong Guo, Xiaoshun He · 发表于：Clinical Cancer Research · 年份：2025 · DOI：10.1158/1078-0432.ccr-25-1245 · 被引用次数：5 · 研究领域：CAR-T cell therapy research、Microbial Inactivation Methods、Virus-based gene therapy research

PURPOSE: This study aimed to preliminarily evaluate the safety, tolerability, and antitumor efficacy of hepatitis B virus (HBV)-specific T-cell receptor (TCR)-T cell therapy combining mRNA electroporation and lentiviral transduction in patients with recurrent HBV-hepatocellular carcinoma after liver transplantation. PATIENTS AND METHODS: In this pilot study (NCT04677088), two types of autologous HBV-specific TCR-redirected T cells were assessed without prior lymphodepletion: (i) multiple infusions of mRNA-electroporated HBV-TCR-T cells (mRNA-HBV-TCR-T cells) and (ii) one to three infusions of lentiviral-transduced HBV-TCR-T cells (lenti-HBV-TCR-T cells). Treatment-related adverse events were assessed using the Common Terminology Criteria for Adverse Events, and antitumor efficacy was evaluated using CT imaging according to RECIST v1.1 criteria. Progression-free survival (PFS) was defined as the time from the start of study treatment until objective tumor progression or death. RESULTS: Both mRNA-electroporated and lentiviral-transduced HBV-specific TCR-T cells demonstrated a favorable safety profile, with only grade 1 to 2 treatment-related adverse events observed. In the mRNA-HBV-TCR-T cells cohort, the median PFS was 2.32 months (range, 1.87-2.77 months). The combination therapy cohort (mRNA-HBV-TCR-T cells + lenti-HBV-TCR-T cells) showed a median PFS of 7.34 months (range, 4.47-7.60 months). CT imaging indicated effective tumor control in the combination therapy group. CONC...