CAR T Cell Therapy for Rheumatoid Arthritis

Chimeric Antigen Receptor (CAR) T cell therapy has revolutionised the treatment of relapsed/refractory B cell leukaemia, lymphoma and multiple myeloma through targeting of CD19 and BCMA antigens on the surface of these cells. A growing body of evidence has recently demonstrated that these cell-based therapies can also target autoimmune diseases including systemic lupus erythematosus, systemic sclerosis, neuromyelitis optica spectrum disorder, myasthenia gravis, idiopathic inflammatory myositis, multiple sclerosis and rheumatoid arthritis. To date, ten patients with rheumatoid arthritis have been treated with CAR T cells targeting CD19/CD20 or BCMA antigens on B cells. Nine patients with seropositive disease have shown remarkable responses, including depletion of circulating B cells, ablation of autoantibody levels and drug-free remission. A tenth patient with seronegative disease initially responded to CAR T cell therapy but later relapsed. This review provides in-depth analysis of these single case studies and highlights emerging in-vitro and animal model studies where T cell subsets have been engineered with CARs to fine-tune their immune responses for the treatment of rheumatoid arthritis, including targeting of autoreactive B cells, autoreactive T cells or fibroblasts. CAR T cell therapy holds enormous promise for the treatment of difficult-to-treat rheumatoid arthritis, but more research and large clinical trials are needed to confirm its efficacy and safety.