Engineering virus-specific T cells that target HBV infected hepatocytes and hepatocellular carcinoma cell lines

J Hepatol. 2011 Jul;55(1):103-10. doi: 10.1016/j.jhep.2010.10.025. Epub 2010 Nov 23.


Background & aims: Virus-specific T cells capable of controlling HBV and eliminating hepatocellular carcinoma (HCC) expressing HBV antigens are deleted or dysfunctional in patients with chronic HBV or HBV-related HCC. The goal of this study was to determine if T cell receptor (TCR) gene transfer can reconstitute HBV-specific T cell immunity in lymphocytes of chronic HBV patients and investigate whether HCC cells with natural HBV-DNA integration can be recognized by genetically modified T cells.

Methods: We used vector-mediated gene transfer to introduce HLA-A2-restricted, HBV-specific TCRs into T cells of chronic HBV as well as HBV-related HCC patients.

Results: The introduced TCRs were expressed on the cell surface, evidenced by Vβ and pentamer staining. TCR transduced T cells produced IFN-γ, TNF-α, IL-2, and lysed HBV infected hepatocyte-like cell lines. Furthermore, HCC cell lines with natural HBV-DNA integration could be recognized by HBV-specific TCR-re-directed T cells.

Conclusions: TCR re-directed HBV-specific T cells generated from PBMC of chronic HBV and HBV-related HCC patients were multifunctional and capable of recognizing HBV-infected cells and HCC tumor cells expressing viral antigens from naturally integrated HBV DNA. These genetically modified T cells could be used to reconstitute virus-specific T cell immunity in chronic HBV patients and target tumors in HBV-related HCC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Hepatocellular / immunology*
  • Carcinoma, Hepatocellular / virology*
  • Cell Line
  • Cell Line, Tumor
  • Gene Expression
  • Genetic Engineering
  • Genetic Vectors
  • HLA-A2 Antigen / metabolism
  • Hepatitis B Surface Antigens / genetics
  • Hepatitis B Surface Antigens / immunology
  • Hepatitis B virus / immunology*
  • Hepatitis B, Chronic / immunology
  • Hepatitis B, Chronic / virology
  • Humans
  • Immunity, Cellular
  • Liver Neoplasms / immunology*
  • Liver Neoplasms / virology*
  • Receptors, Antigen, T-Cell / genetics
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / virology*
  • Transduction, Genetic


  • HLA-A2 Antigen
  • Hepatitis B Surface Antigens
  • Receptors, Antigen, T-Cell