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