Chimeric Antigen Receptor T Cell Therapy in Systemic Lupus Erythematosus: Mechanisms, Clinical Advances, and Future Directions a Comprehensive Review
Ahmad Matarneh, Bayan Matarneh, Omar Salameh, Abdelrauof Akkari, Nasrollah Ghahramani, Naman Trivedi
Abstract
Systemic lupus erythematosus (SLE) is a chronic, multisystem autoimmune disorder characterized by loss of self-tolerance, immune complex deposition, and progressive organ damage. Despite advances in immunosuppressive therapy, a subset of patients develops treatment-resistant or refractory manifestations; terms used variably in the literature to describe inadequate response to multiple standard immunosuppressants. Chimeric antigen receptor T cell (CAR-T) therapy, a revolutionary modality in oncology, is now emerging as a promising approach in severe autoimmune diseases including SLE. By redirecting autologous T cells to target B cell antigens such as CD19 or BCMA, CAR-T therapy enables deep and sustained B cell depletion, potentially resetting immune tolerance.Early case series have reported encouraging remission rates and serologic improvements in refractory SLE; however, these observations derive from small, uncontrolled studies. The long-term durability, relapse risk, safety profile, and cost-effectiveness of CAR-T therapy in autoimmune disease remain uncertain and require confirmation in larger, controlled trials. This narrative review synthesizes the current understanding of CAR-T therapy in SLE, covering immunopathogenesis, rationale for B cell targeting, CAR-T mechanisms, preclinical evidence, clinical outcomes, safety considerations, and future directions. We integrate data from peer-reviewed studies, conference abstracts, and preprints up to August 2025, and propose a framework for integrating CAR-T into the treatment paradigm for refractory SLE.