title: Engineering virus-specific T cells that target HBV infected hepatocytes and hepatocellular carcinoma cell lines.
abstract: OBJECTIVE
  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.
authors.affiliation: Singapore Institute for Clinical Sciences, Agency for Science Technology and Research, Singapore.
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Gehring
authors.forename: Shao-An
authors.initials: SA
authors.lastname: Xue
authors.forename: Zi Zong
authors.initials: ZZ
authors.lastname: Ho
authors.forename: Denise
authors.initials: D
authors.lastname: Teoh
authors.forename: Christiane
authors.initials: C
authors.lastname: Ruedl
authors.forename: Adeline
authors.initials: A
authors.lastname: Chia
authors.forename: Sarene
authors.initials: S
authors.lastname: Koh
authors.forename: Seng Gee
authors.initials: SG
authors.lastname: Lim
authors.forename: Mala K
authors.initials: MK
authors.lastname: Maini
authors.forename: Hans
authors.initials: H
authors.lastname: Stauss
authors.forename: Antonio
authors.initials: A
authors.lastname: Bertoletti
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000276:immunology* / Q000821:virology*; D002460:Cell Line; D045744:Cell Line, Tumor; D015870:Gene Expression; D005818:Genetic Engineering; D005822:Genetic Vectors; D015789:HLA-A2 Antigen / Q000378:metabolism; D006514:Hepatitis B Surface Antigens / Q000235:genetics / Q000276:immunology; D006515:Hepatitis B virus / Q000276:immunology*; D019694:Hepatitis B, Chronic / Q000276:immunology / Q000821:virology; D006801:Humans; D007111:Immunity, Cellular; D008113:Liver Neoplasms / Q000276:immunology* / Q000821:virology*; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology* / Q000821:virology*; D014161:Transduction, Genetic
chemical_list: D015789:HLA-A2 Antigen; D006514:Hepatitis B Surface Antigens; D011948:Receptors, Antigen, T-Cell