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

[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.

[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.