MI2025 – Anthony Tan

Title:
mRNA based T cell engineering for HBV-related Hepatocellular Carcinoma (HBV-HCC)

Abstract:
The clinical efficacy of chimeric antigen and T cell receptor (TCR) T cell immunotherapies has been primarily attributed to their ability to proliferate and provide a consistent effector function over an extended duration. Contrary to this prevailing dogma, we have adoptively transferred HBV-specific TCR T cells (mRNA HBV-TCR), engineered through mRNA electroporation, for the treatment of primary HBV-related HCC (HBV-HCC) patients and showed promising clinical outcome despite their temporally limited function. By studying the immunological features of the treated patients, we observed that complete or partial response to the TCR-T cell treatment occurring in some patients was associated with the triggering of an inflammatory reaction and it was not directly proportional to the quantity and persistence of TCR-T cells infused into the patients. Here we provide preliminary evidence and hypothesize that the efficacy of TCR-T cell therapy against HBV-related HCC can be associated not with their persistence but with an ability to alter the HCC microenvironment and induce novel antitumor T cells.

Biography:
Anthony Tanoto Tan is currently an Assistant Professor in the Emerging Infectious Diseases Programme at Duke-NUS Medical School. His research is focused on understanding the pathogenesis and immune response against Hepatitis B Virus (HBV) infection, with a particular emphasis on the development of T cell-based immunotherapy approaches targeting chronic HBV infection and HBV-related hepatocellular carcinoma (HBV-HCC). He is also engaged in translational research, collaborating with clinical and industry partners to bring laboratory findings to patient care. Notably, he is actively involved in clinical trials in Singapore and China to assess the safety and efficacy of adoptively transferring engineered TCR T cells for HBV-HCC and chronic HBV treatment, in collaboration with Lion TCR Pte. Ltd.

During the SARS-CoV-2 pandemic, he leveraged his expertise in virus-specific T cell analysis to characterize and investigate the role of SARS-CoV-2-specific T cells. His work included identifying and characterizing these T cells in both the peripheral blood and the upper respiratory tract of individuals and contributed to the broader understanding of T cell-mediated immunity in COVID-19 disease and vaccination. This series of research led to the development of a rapid whole blood cytokine release assay for evaluating antigen-specific T cell responses against various viral diseases. This assay is now being used to monitor the functionality of HBV-specific T cells and the adoptively transferred engineered HBV-TCR T cells in patients with HBV-related HCC.