Antonio Bertoletti

Professor

Email

Contact: 66013574

Bio Research Publications

Antonio Bertoletti, MD is an expert in the field of viral hepatitis, with a specific interest in the immunopathogenesis of HBV infection. He began working in viral hepatitis as a medical student 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 for the first time the Hepatitis B virus (HBV) specific cytotoxic T cell response in man. He returned to the University of Parma, where he worked in the Department of Infectious Diseases as a Clinical Scientist continuing his study of human HBV specific T cells. Dr. Bertoletti then joined (1995) the MRC Unit in the Gambia, as Senior Immunologist, to study HIV-2 specific T cell Immunity before accepting a position of Senior Lecturer at “The UCL Institute of Hepatology” at University College of London (UK) (1997). 

In 2006 he moved to Singapore where he was the Director of Infection and Immunity Program at the Singapore Institute for Clinical Sciences (A*STAR) until 2013 before moving, as Full Professor, at the Emerging Viral Disease Program at Duke-NUS Medical School. He also maintains an Adjunct Position at the Singapore Immunology Network, (A*STAR). He won for two consecutive terms the Singapore Translational Research Awards (2013 and 2018).

In 2015 he founded Lion TCR Pte (http://liontcr.com), a biotech company developing immune-based treatments for virus-related cancers (HBV-HCC and EBV related malignancies) and chronic viral infections. This immune therapy utilizes T cell receptors engineered T cells targeting viral antigens express in cancer cells. The company has been the first to initiate and run clinical trials (Phase I and II) for the treatment of HBV-related HCC relapses in liver transplant patients and in primary HCC in Singapore and China. At present he is Chairman of the Board and major shareholder.

His current research is focus on the development of new immunological based therapies (TCR-redirected T cells) for the treatment of HBV chronic infection and Hepatocellular carcinoma and on the characterization of antiviral Immunity in chronic HBV patients. In the last 2 years, after the start of the COVID-19  pandemic, his laboratory has been actively involved in the characterization of SARS-COV2 specific T cell immune response (Le Bert et al, Nature 2020, 584: 457-62)  in COVID-19 and SARS convalescent and healthy individuals. 

 

Our laboratory focuses on understanding how HBV infection evades or triggers the host-immunity that causes viral control and/or liver inflammation.

These immune mechanisms are preferentially studied in patient’s samples directly (peripheral blood and liver biopsies), obtained with active collaborations with different clinical groups. We also utilize human-chimeric SCID mouse reconstituted with human hepatocytes and immune cells that mimics HBV infection.

Our major projects are focused on:

  • Adoptive T-cell Therapy
    • This focuses on TCR-redirected T cells that can recognize and target Hepatitis B virus in order to reconstitute HBV-specific Immunity in patients with chronic Hepatitis B or Hepatocellular Carcinoma (HCC). We are also working on ways to improve the efficacy of these engineered cells and the selection of the correct TCR for personalized treatment of HBV-related HCC patients. Understanding the liver microenvironment and how it affects the behavior of T-cell receptor engineered T cells is crucial in order for adoptive cell therapy approaches to be successful in the treatment of chronic HBV infection or related hepatocellular carcinoma. We have developed an imaging-based 3-dimensional microdevice assay in collaboration as a pre-clinical test bench to evaluate the functionality of engineered T cells in environments similar to that encountered during actual adoptive therapy.
  • 3-Dimensional Microfluidics Platform 
    • Adaptive immune response in HBV infection and how it might evolve and mature over time; this includes the humoral compartment in which the role of B-cells in HBV infection is relatively poorly understood, and cell-mediated immunity in which T-cells are important for anti-viral control. Understanding the mechanism of HBV vertical infection (mother to child) and the impact that HBV infection exert on the maturation of the host immune system.
  • Adaptive immune response in HBV infection and how it might evolve and mature over time; this includes the humoral compartment in which the role of B-cells in HBV infection is relatively poorly understood, and cell-mediated immunity in which T-cells are important for anti-viral control.
  • Understanding the mechanism of HBV vertical infection (mother to child) and the impact that HBV infection exert on the maturation of the host immune system

Articles:

1 Lim, J. M. E. et al. SARS-CoV-2 breakthrough infection in vaccinees induces virus-specific nasal-resident CD8+ and CD4+ T cells of broad specificity. J Exp Med 219 (2022). https://doi.org:10.1084/jem.20220780

2 Lim, J. M. E. et al. A comparative characterization of SARS-CoV-2-specific T cells induced by mRNA or inactive virus COVID-19 vaccines. Cell Rep Med 3, 100793 (2022). https://doi.org:10.1016/j.xcrm.2022.100793

3 Qui, M. et al. Favorable vaccine-induced SARS-CoV-2-specific T cell response profile in patients undergoing immune-modifying therapies. J Clin Invest 132 (2022). https://doi.org:10.1172/JCI159500

4 Tan, A. T. et al. Early induction of functional SARS-CoV-2-specific T cells associates with rapid viral clearance and mild disease in COVID-19 patients. Cell Rep 34, 108728 (2021). https://doi.org:10.1016/j.celrep.2021.108728

5 Tan, A. T. et al. Rapid measurement of SARS-CoV-2 spike T cells in whole blood from vaccinated and naturally infected individuals. J Clin Invest 131 (2021). https://doi.org:10.1172/JCI152379

6 Le Bert, N. et al. Highly functional virus-specific cellular immune response in asymptomatic SARS-CoV-2 infection. J Exp Med 218 (2021). https://doi.org:10.1084/jem.20202617

7 Le Bert, N. et al. SARS-CoV-2-specific T cell immunity in cases of COVID-19 and SARS, and uninfected controls. Nature 584, 457-462 (2020). https://doi.org:10.1038/s41586-020-2550-z


Reviews:


Bertoletti, A., Le Bert, N. & Tan, A. T. SARS-CoV-2-specific T cells in the changing landscape of the COVID-19 pandemic. Immunity 55, 1764-1778 (2022). https://doi.org:10.1016/j.immuni.2022.08.008

Bertoletti, A., Le Bert, N., Qui, M. & Tan, A. T. SARS-CoV-2-specific T cells in infection and vaccination. Cell Mol Immunol 18, 2307-2312 (2021). https://doi.org:10.1038/s41423-021-00743-3