HBsAg-redirected T cells exhibit antiviral activity in HBV-infected human liver chimeric mice

Cytotherapy. 2018 May;20(5):697-705. doi: 10.1016/j.jcyt.2018.02.002. Epub 2018 Apr 6.


Background: Chronic hepatitis B virus (HBV) infection remains incurable. Although HBsAg-specific chimeric antigen receptor (HBsAg-CAR) T cells have been generated, they have not been tested in animal models with authentic HBV infection.

Methods: We generated a novel CAR targeting HBsAg and evaluated its ability to recognize HBV+ cell lines and HBsAg particles in vitro. In vivo, we tested whether human HBsAg-CAR T cells would have efficacy against HBV-infected hepatocytes in human liver chimeric mice.

Results: HBsAg-CAR T cells recognized HBV-positive cell lines and HBsAg particles in vitro as judged by cytokine production. However, HBsAg-CAR T cells did not kill HBV-positive cell lines in cytotoxicity assays. Adoptive transfer of HBsAg-CAR T cells into HBV-infected humanized mice resulted in accumulation within the liver and a significant decrease in plasma HBsAg and HBV-DNA levels compared with control mice. Notably, the fraction of HBV core-positive hepatocytes among total human hepatocytes was greatly reduced after HBsAg-CAR T cell treatment, pointing to noncytopathic viral clearance. In agreement, changes in surrogate human plasma albumin levels were not significantly different between treatment and control groups.

Conclusions: HBsAg-CAR T cells have anti-HBV activity in an authentic preclinical HBV infection model. Our results warrant further preclinical exploration of HBsAg-CAR T cells as immunotherapy for HBV.

Keywords: CAR T cells; adoptive immunotherapy; hepatitis B virus.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Antiviral Agents / immunology*
  • Chimera / immunology*
  • Hep G2 Cells
  • Hepatitis B Surface Antigens / metabolism*
  • Hepatitis B virus / physiology*
  • Hepatitis B, Chronic
  • Humans
  • Immunotherapy / methods
  • Liver / immunology*
  • Liver / virology*
  • Mice
  • Receptors, Antigen, T-Cell / immunology
  • Receptors, Chimeric Antigen / metabolism
  • T-Lymphocytes / immunology*
  • Virion / metabolism


  • Antiviral Agents
  • Hepatitis B Surface Antigens
  • Receptors, Antigen, T-Cell
  • Receptors, Chimeric Antigen