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.
Immunologists, Oncologists and Researchers who are interested in:
Professor Antonio Bertoletti, M.D.
Duke-Nus Medical School and Co Founder Lion TCR
Antonio Bertoletti, MD is an expert in the field of viral hepatitis. He has been working on viral hepatitis since his medical student days at the University of Parma, Italy. During his MD specialization (1991) in Infectious Diseases, he spent two years at The Scripps Research Institute, La Jolla characterizing the inaugural Hepatitis B virus (HBV) specific cytotoxic T cells in human. Upon returning to the University of Parma, he worked in the Department of Infectious Diseases as a Clinical Scientist to continue his study on human HBV specific T cells (1991-1997) before joining The Institute of Hepatology at University College of London, UK (1997). In 2006, he relocated to Singapore where he was appointed as the Director of Infection and Immunity Program at the Singapore Institute for Clinical Sciences (A*STAR) until 2013 before joining the Emerging Infectious Disease Program at Duke-NUS Medical School. In 2015, he co-founded Lion TCR Pte. Ltd. with Dr Li Lietao, a biotech company developing new immune based treatment for virus-related cancers (HBV-HCC and EBV related malignancies) and chronic viral infections. His research interest is in immunopathogenesis of HBV infection. Currently, he is focusing on understanding the impact of age in HBV infection/pathology and the development of new immunological based therapies (TCR-redirected T cells) for the treatment of HBV and Hepatocellular carcinoma.
Research and disease areas