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T cells redirected by a chimeric antigen receptor recognizing HBsAg efficiently control HBV in vivo in transgenic mice

      Current antivirals suppress HBV but do not clear the infection. For virus clearance strong effector T cell responses are needed, which are sparse in chronically infected individuals. Cell therapy using T cells redirected by HBV-specific receptors may clear HBV and help to prevent and treat HBV-associated liver cancer. We designed a chimeric antigen receptor (CAR) that is composed of a single chain antibody fragment binding to HBsAg and CD28 / CD3ζ signaling domains. This study aimed to proof feasibility of this approach in vivo addressing the following challenges: (i) T cell-depletion to generate space for cell engraftment in chronic virus carriers is too perilous, (ii) viral antigens circulating in high amounts may inactivate transferred T cells or (iii) trigger uncontrolled immune damage.
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