Advancing CD19 CAR T Cell Therapy for Treatment of Primary Biliary Cholangitis

Abstract CD19 Chimeric Antigen Receptor (CAR) T cell therapy is emerging as a revolutionary approach in autoimmune disease management, offering a promising alternative to conventional treatments like anti-CD20 antibody therapy. Unlike challenges associated with existing therapies, CD19 CAR T cells, engineered to recognize CD19 molecules on B cells, exhibit remarkable efficacy in achieving targeted B cell depletion. Upon target recognition, they become activated, efficiently eliminating the harmful B cells. Furthermore, the CAR T cells exhibit a propensity for proliferation upon target recognition, thereby ensuring their prolonged presence within the body. Our findings unequivocally establish the effectiveness of CD19 CAR T cells in specifically targeting and depleting B cells, both in vitro and in vivo. In a well-established PBC model involving NOD.c3 mice, the application of CD19 CAR T cell therapy led to a remarkable reduction in liver pathology scores, indicating a substantial decrease in tissue damage and inflammation compared to control groups. Beyond liver autoimmunity, our research holds promise for treating other autoimmune conditions where B cells play a detrimental role. These insights pave the way for innovative therapies that have the potential to revolutionize autoimmune disease management, offering a hope for affected individuals and improving their quality of life.