Advancements and challenges in CAR T cell therapy in autoimmune diseases

Chimeric antigen receptor (CAR) T cells are highly effective at targeting and eliminating cells of the B cell lineage. CAR T cell therapy has become a standard-of-care treatment for patients with relapsed or refractory B cell malignancies. In addition, the administration of genetically modified T cells with the capacity to deplete B cells and/or plasma cells has tremendous therapeutic potential in autoimmune diseases. In the past few years, CD19-based and B cell maturation antigen (BCMA)-based CAR T cell therapies have been applied to various B cell-mediated autoimmune diseases including systemic lupus erythematosus, idiopathic inflammatory myopathy, systemic sclerosis, neuromyelitis optica spectrum disorder, myasthenia gravis and multiple sclerosis. The scientific rationale behind this approach is that deep depletion of B cells, including autoreactive B cell clones, could restore normal immune function, referred to as an immune reset. In this Review, we discuss important aspects of CAR T cell therapy in autoimmune disease, including considerations relating to patient selection, safety, efficacy and medical management. These considerations are based on the early experiences of CAR T cell therapy in autoimmune diseases, and as the field of CAR T cell therapy in autoimmune diseases continues to rapidly evolve, these issues will remain subject to ongoing refinement and adaptation. CAR T cell therapy shows promise for achieving long-term drug-free remission in various autoimmune diseases. This Review discusses the ongoing challenges and unanswered questions of CAR T cell therapy in autoimmune diseases, including pre-procedural, procedural and post-procedural considerations. Chimeric antigen receptor (CAR)-expressing cells provide a new and powerful treatment strategy for severe forms of various autoimmune diseases.The CAR-expressing cells applied so far have typically been T cells that recognize B cell-specific or plasma cell-specific antigens such as CD19 or BCMA (B cell maturation antigen), respectively.Currently, most information on the treatment of autoimmune disease with CAR-expressing cells comes from the treatment of patients with autologous CD19-targeting CAR T cells.The success of treating autoimmune disease with CAR-expressing cells is dependent on various pre-procedural, procedural and post-procedural factors; these factors are important considerations that warrant further investigation in future studies.Critical patient selection and careful monitoring for both efficacy and toxicity are paramount for successful treatment with CAR-expressing cells.