CAR T-cell therapy for systemic lupus erythematosus: current status and future perspectives

Abstract

Systemic lupus erythematosus (SLE) and lupus nephritis (LN) are debilitating autoimmune disorders characterized by pathological autoantibodies production and immune dysfunction, causing chronic inflammation and multi-organ damage. Despite current treatments with antimalarial drugs, glucocorticoids, immunosuppressants, and monoclonal antibodies, a definitive cure remains elusive, highlighting an urgent need for novel therapeutic strategies. Recent studies indicate that chimeric antigen receptor T-cell (CAR-T) therapy has shown promising results in treating B-cell malignancies and may offer a significant breakthrough for non-malignant conditions like SLE. In this paper, we aim to provide an in-depth analysis of the advancements in CAR-T therapy for SLE, focusing on its potential to revolutionize treatment for this complex disease. We explore the fundamental mechanisms of CAR-T cell action, the rationale for its application in SLE, and the immunological underpinnings of the disease. We also summarize clinical data on the safety and efficacy of anti-CD19 and anti-B cell maturation antigen (BCMA) CAR-T cells in targeting B-cells in SLE. We discuss the clinical implications of these findings and the potential for CAR-T therapy to improve outcomes in severe or refractory SLE cases. The integration of CAR-T therapy into the SLE treatment paradigm presents a new horizon in autoimmunity research and clinical practice. This review underscores the need for continued exploration and optimization of CAR-T strategies to address the unmet needs of SLE patients.