Targeted delivery of interferon-α to hepatitis B virus-infected cells using T-cell receptor-like antibodies

Hepatology. 2012 Dec;56(6):2027-38. doi: 10.1002/hep.25875. Epub 2012 Jul 12.


During antiviral therapy, specific delivery of interferon-α (IFNα) to infected cells may increase its antiviral efficacy, trigger a localized immune reaction, and reduce the side effects caused by systemic administration. Two T-cell receptor-like antibodies (TCR-L) able to selectively bind hepatitis B virus (HBV)-infected hepatocytes of chronic hepatitis B patients and recognize core (HBc18-27) and surface (HBs183-91) HBV epitopes associated with different human leukocyte antigen (HLA)-A*02 alleles (A*02:01, A*02:02, A*02:07, A*02:11) were generated. Each antibody was genetically linked to two IFNα molecules to produce TCR-L/IFNα fusion proteins. We demonstrate that the fusion proteins triggered an IFNα response preferentially on the hepatocytes presenting the correct HBV-peptide HLA-complex and that the mechanism of the targeted IFNα response was dependent on the specific binding of the fusion proteins to the HLA/HBV peptide complexes through the TCR-like variable regions of the antibodies.

Conclusion: TCR-L antibodies can be used to target cytokines to HBV-infected hepatocytes in vitro. Fusion of IFNα to TCR-L decreased the intrinsic biological activity of IFNα but preserved the overall specificity of the protein for the cognate HBV peptide/HLA complexes. This induction of an effective IFNα response selectively in HBV-infected cells might have a therapeutic advantage in comparison to the currently used native or pegylated IFNα.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Viral / immunology
  • Antibodies, Viral / pharmacology*
  • Antiviral Agents / pharmacology*
  • Artificial Gene Fusion
  • CD8-Positive T-Lymphocytes / drug effects
  • Chemokines / metabolism
  • Drug Carriers / pharmacology
  • HLA-A Antigens / immunology*
  • Hep G2 Cells
  • Hepatitis B / drug therapy
  • Hepatitis B / immunology*
  • Hepatitis B / virology
  • Hepatitis B virus / genetics
  • Hepatitis B virus / immunology*
  • Humans
  • Interferon-alpha / pharmacology*
  • Lymphocyte Activation / drug effects
  • Mice
  • Recombinant Fusion Proteins / pharmacology*


  • Antibodies, Viral
  • Antiviral Agents
  • Chemokines
  • Drug Carriers
  • HLA-A Antigens
  • Interferon-alpha
  • Recombinant Fusion Proteins