Functional attributes of responding T cells in HCV infection: The recent advances in engineering functional antiviral T cells

Abstract

Hepatitis C virus (HCV) is one of the major causes of hepatocellular carcinoma (HCC) around the world. HCV promotes characteristics of cancer stem cells and the infected cells are insensitive to apoptotic signals, which lead to persistent antigen stimulation and T cell exhaustion in the host. In spite of new effective antiviral drugs, new challenges are around the corner as drug-resistant viral strains and drug-drug interactions have already been reported. Considering that there are few effective treatments available for HCC, novel immunotherapies to prevent HCC and late stage HCV-related liver diseases should be considered. Given that adoptive immunotherapy with antigen-specific T lymphocytes has emerged as an effective therapeutic strategy for combating cancer, there is, therefore, reason to examine the possibility of using highly functional HCV-reactive T cells in immunotherapy. This review aims to provide the current understanding of natural HCV responding T cells in HCV infection and to give an update on the novel approaches that have the capacity to ex vivo generate functional T cells for potential adoptive cell therapy. Approaches based on the pMHC tetramer-associated magnetic enrichment, exogenous HCV T cell receptor transfer, and induced pluripotent stem cell technologies are described herein. Their potentials as immunotherapeutic against HCV-related diseases are discussed. © 2013 L. Hirszfeld Institute of Immunology and Experimental Therapy, Wroclaw, Poland.