T-Cell Receptor Re-directed Therapy
Adoptive cell therapy using a patient’s own T cells redirected to recognize and target hepatitis B virus is a promising approach to reconstitute HBV-specific immunity in patients with chronic hepatitis B and/or HBV-related hepatocellular carcinoma.
To overcome the potential problem of T cell toxicities (i.e. T cell-mediated liver damage) and for practical concerns, we used electroporation of messenger RNA (mRNA) encoding HBV-specific T-cell receptor (TCR) in human primary T cells to transiently redirect their specificity.
3D Micro Fluidics Platform
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. In collaboration with Biosym (SMART-MIT, Singapore), we have developed an imaging-based 3-dimensional microdevice assay as a pre-clinical test bench to evaluate the functionality of engineered T cells in environments similar to that encountered during actual adoptive therapy.
Modeling of HBV Infection in vitro
Yang Ning Han
Our research interest lies in modeling HBV infection in vitro in order to understand the interactions between HBV infected hepatocytes and HBV specific T cells. Understanding viral antigen presentation and the kinetics of HBV specific T cell responses upon HBV infection in vitro can then lead to further insights into immunological events during HBV infection in vitro.
T-Cell Responses During HBV Infection
Nina Le Bert
We are investigating the T cell component of the immune response to HBV to better understand the role of these cells in protection and/or liver pathology during chronic HBV infection. We are using different approaches from ELISPOT, FACS to CyTOF (in collaboration with Dr. Evan Newell, SIGN). We are studying T cells circulating in the peripheral blood and those present in HBV-infected livers. T cell responses are also compared across patients of different age groups (adolescents versus adults), since the disease profiles appear to be extremely different in these patients.
Liver Immune Microenvironment
Alfonso Tan Garcia
We aim to understand the immunological changes that occur within the liver during chronic HBV infection in humans. In collaboration with the Humanized Mouse Unit (Institute of Molecular and Cell Biology), we are also characterizing a humanized mouse model of HBV infection, in order to develop an in vivo system for mechanistic and therapeutic studies.
The Impact Of Vertical HBV Infection On Immune System Maturity
Vertical (mother-to-child) transmission is the major cause of hepatitis B virus (HBV) infection in children in Asia. The goal of this project is to gain an understanding of the key components of the immune response to HBV present in neonates and children of HBV-infected mothers, which in turn, will provide information about the cause of HBV chronicity in Asian patients and in the management of baby born to HBsAg+ mothers.