Chronic Viral Liver Diseases: Approaching the Liver Using T Cell Receptor-Mediated Gene Technologies

Abstract

Chronic infection with viral hepatitis is a major risk factor for liver injury and hepatocellular carcinoma (HCC). One major contributing factor to the chronicity is the dysfunction of virus-specific T cell immunity. T cells engineered to express virus-specific T cell receptors (TCRs) may be a therapeutic option to improve host antiviral responses and have demonstrated clinical success against virus-associated tumours. This review aims to give an overview of TCRs identified from viral hepatitis research and discuss how translational lessons learned from cancer immunotherapy can be applied to the field. TCR isolation pipelines, liver homing signals, cell type options, as well as safety considerations will be discussed herein.

Human MAIT cells endowed with HBV specificity are cytotoxic and migrate towards HBV-HCC while retaining antimicrobial functions

“…Unlike other human T cell types, MAIT cell potential for liver-targeted immunotherapy is largely unexplored. 31 , 32 Here, we employ a recently established protocol 33 to investigate TCR-redirected MAIT cells in the context of HBV using a preclinical HCC cell model. Our findings are relevant for the application of TCR-redirected MAIT cells for immunotherapy of liver diseases.…”

T Cell Repertoire During Ontogeny and Characteristics in Inflammatory Disorders in Adults and Childhood

“…It could be demonstrated that investigations in the TCR repertoire can help to develop new biomarkers. Furthermore, new therapeutic options were established in cancer therapy using engineered T cell subsets ( 78 , 79 ). Whether these advantages are suitable for clinical application and could be transferred to chronic infections and autoinflammatory diseases is still a topic of research ( 80 ).…”

The pathogenesis of liver cancer and the therapeutic potential of bioactive substances

“…In chronic viral hepatitis, the development of fibrosis, cirrhosis, and HCC is associated with the immune response against the infected liver ( Zambam de Mattos et al, 2021 ). Disturbances in the function of virus-specific T cells are a major factor underlying the incapacity of the immune response to clear infected cells on the one hand, and on the other hand, it influences the development of the disease ( Healy et al, 2020 ). Cytotoxic CD8 + T cells are key immune effectors against tumors.…”