Personalized T-cell therapy against HBV infection & HBV-related HCC

Adoptive transfer of lymphocytes expressing engineered T cell receptors (TCRs) is a promising immunotherapeutic option which specifically targets antigens from viral-infected cells and tumors. Prof. Bertoletti and his team engineered a library of TCRs specific for different Hepatitis B Virus (HBV) antigens to generate a pool of HBV-specific TCR-T cells. These TCR-T cells have been shown to recognize HBV epitopes presented on infected hepatocytes and hepatocellular carcinoma (HCC) cells with HBV-DNA integration in both experimental models and selected patients with HBV-related HCC relapses. However, safety concerns on possible irreversible structural and functional liver damage by cytotoxic TCR-T cells have limited the clinical usage of this immunotherapeutic approach. To overcome this limitation, they selected patients with HCC relapses after liver transplantation for immunotherapy since TCR-T cells only target HBV epitopes presented on HCC-relapses. Moreover, they also modified TCR-T cell production methods to reduce cytotoxicity and life span of TCR-T cell. These strategies that lead to the successful production of safe TCR-T cell effectors for immunotherapy of HBV infection and HBV-related cancers will be discussed in this webinar.