CAR-T cells targeting activated hepatic stellate cells ameliorate liver fibrosis in mouse models

Background & Aims The transition to liver fibrosis represents a crucial and irreversible transition in chronic liver diseases, with liver fibrosis being a key driver of the progression to life-threatening complications, including cirrhosis and hepatocellular carcinoma (HCC). However, effective pharmacological therapies for liver fibrosis are lacking. Our study investigated the role of chimeric antigen receptor (CAR)-T cells in targeting and eliminating activated hepatic stellate cells (HSCs) for the treatment of liver fibrosis. Methods We engineered CAR-T cells targeting fibroblast activation protein (FAP), a cell surface protein specifically overexpressed on activated HSCs, and evaluated their therapeutic effects on liver fibrosis across four different mouse models. Results FAP CAR-T therapy significantly alleviated liver fibrosis across multiple etiologies ( p