HBV-Specific TCR-T Cell Therapy Combining mRNA Electroporation and Lentiviral Transduction: Treatment Regime for Recurrent HBV-Related HCC Post—Liver Transplantation

Abstract Background & aims: This study aimed to preliminarily evaluate the safety, tolerability, and antitumor efficacy of HBV-specific TCR-T cell therapy combining mRNA electroporation and lentiviral transduction in patients with recurrent HBV-HCC post-LT. Methods: In this pilot study (NCT04677088), two types of autologous HBV-specific TCR-redirected T cells were assessed without prior lymphodepletion: (1) multiple infusions of mRNA-electroporated HBV-TCR-T cells (mRNA-HBV-TCR-T cells) and (2) 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 (CTCAE), and anti-tumor efficacy was evaluated using computed tomography (CT) imaging according to RECIST 1.1 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 to 2.77 months). The combination therapy cohort (mRNA-HBV-TCR-T cells + lenti-HBV-TCR-T cells) showed median PFS of 7.34 months (range: 4.47 to 7.60 months). CT imaging indicated effective tumor control in the combination therapy group. Conclusions: This study preliminarily suggests that the combination of mRNA-HBV-TCR-T cells and lenti-HBV-TCR-T cells could be a safe and potentially effective approach for treating patients following liver transplantation in the context of lifelong immunosuppression drug administration. Further studies are needed to refine treatment strategies and assess long-term safety and efficacy in this special patient population.