Resetting autoimmune disease with CAR cell therapies

Pathogenic B cell activation underlies many autoimmune diseases (AIDs), and their depletion is an attractive therapeutic approach. Chimeric antigen receptor (CAR)-expressing cells-initially developed and successfully used to treat certain cancers-are increasingly being developed to selectively deplete B cells and 'reset' the immune system in AIDs. In this Review, we survey this fast-developing field, providing insights on the current unmet needs in the treatment of AIDs and how CAR T cells could address these needs. In particular, we explore the concept of deep B cell depletion, discuss the currently available technologies and review the key targets (CD19 and B cell maturation antigen) relevant for the treatment of AIDs. We summarize current evidence on the efficacy, safety, risks and limitations of autologous and allogeneic CAR T cells in this setting. Finally, we discuss the future outlook-from a technological and clinical standpoint-for development of engineered CAR-expressing cell therapies for AIDs.