PreS1-targeting chimeric antigen receptor T cells diminish HBV infection in liver humanized FRG mice

Current therapies control but rarely achieve a cure for hepatitis B virus (HBV) infection. Restoration of the HBVspecific immunity by cell-based therapy represents a potential approach for a cure. In this study, we generated HBV specific CAR T cells based on an antibody 2H5-A14 targeting a preS1 region of the HBV large envelope protein. We show that the A14 CAR T cell is capable of killing hepatocytes infected by HBV with high specificity; adoptive transfer of A14 CAR T cells to HBV infected humanized FRG mice resulted in reductions of all serum and intrahepatic virological markers to levels below the detection limit. A14 CAR T cells treatment increased the levels of human IFN-& gamma;, GM-CSF, and IL-8/CXCL-8 in the mice. These results show that A14 CAR T cells may be further developed for curative therapy against HBV infection by eliminating HBV-infected hepatocytes and inducing production of pro-inflammatory and antiviral cytokines.

Automated summary

Researchers generated HBV-specific CAR T cells based on an antibody 2H5-A14 targeting the PreS1 region of the HBV large envelope protein and showed that A14 CAR T cells have a highly specific killing effect on HBV-infected hepatocytes. Adoptive transfer of A14 CAR T cells to HBV-infected humanized FRG mice resulted in significant reductions of all serum and intrahepatic virological markers. A14 CAR T cell treatment also increased the levels of human IFN-γ, GM-CSF, and IL-8/CXCL-8 in the mice. These findings suggest that A14 CAR T cells may be further developed for curative therapy against HBV infection by eliminating infected hepatocytes and inducing the production of pro-inflammatory and antiviral cytokines.