Chimeric antigen receptors: "CARs" in the fast lane for rheumatology

Abstract

Purpose of reviewRecent advances in hematology-oncology have pioneered cell-mediated elimination of pathologic B-cell populations employing chimeric antigen receptor (CAR) T cells. In this review, we discuss recent adoption of CAR-T treatment for severe refractory autoimmune disease. We highlight unique aspects of the autoimmune model and review current clinical data regarding treatment of rheumatologic disease.Recent findingsTo date, several CAR-Ts are FDA approved for Multiple Myeloma and B-cell malignancies and have demonstrated extraordinary clinical responses in refractory disease. Realizing the central role of B-cells in certain autoimmune diseases, CAR-T is now being explored for achieving drug-free remission induction, and potentially cure, of several rheumatologic diseases. The largest experience to date in the field of autoimmunity, building off the University Hospital Erlangen groups' earlier success treating a single patient with CD19-CAR in severe refractory SLE, Mackensen et al. enrolled five patients in a compassionate use program. Following autologous CD19-CAR T infusion, they demonstrated drug-free clinical and laboratory remission for at least 12 months in all five patients, with reconstitution of B cells expressing a naïve phenotype.SummaryCAR-T treatment has shown striking drug-free responses in severe lupus and other autoimmune diseases, creating a need for further exploration and development.