CAR T-cell therapy in autoimmune diseases: where are we and where are we going?

Chimeric antigen receptor (CAR)-based therapies developed for the treatment of haematological malignancies have recently been repurposed to treat refractory systemic autoimmune diseases. In this Review we critically discuss the current data available on the use of CAR-based therapy in systemic autoimmune diseases, the current challenges, and the potential next steps toward their implementation into clinical practice. Beyond the targeting of B cells via CD19, we discuss the advantages and potential pitfalls of targeting plasma cells (B-cell Maturation Antigen or CD138) and other non-immune targets, such as fibroblast activated protein, and of aiming to restore immune homeostasis using CAR T regulatory cells. Crucial points need to be addressed for CAR-based therapy to become a viable treatment option for patients with systemic autoimmune diseases.