Exosome-based strategies to enhance CAR-T cell therapy for systemic lupus erythematosus: A promising new frontier

Dysregulated B lymphocyte activation plays a pivotal role in the pathogenesis of systemic lupus erythematosus (SLE), making it a promising target for therapeutic intervention. Chimeric antigen receptor T cell (CAR-T) therapy, specifically targeting CD19-positive B cells, has shown potential in selectively eliminating aberrant B cells, offering a path toward sustained remission and even complete eradication of SLE. However, the broad immunosuppressive effects and cytotoxicity associated with CAR-T therapy pose significant challenges to its application in autoimmune disease treatment. Recent advances in extracellular vesicle biology, particularly exosomes, have highlighted their potential as a cell-free therapeutic platform due to their superior biocompatibility, plasticity, and ability to modulate immune responses. CAR-T-derived or engineered exosomes represent a potential cell-free alternative to reduce cellular dose and toxicity while preserving efficacy in SLE. This review provides a comprehensive analysis of the current landscape of CAR-T cell therapy in autoimmune diseases, with a focus on its safety, effectiveness, and potential in treating SLE. Furthermore, it explores the emerging role of exosomes as a promising adjunct to traditional CAR-T therapy, offering novel perspectives and therapeutic strategies for SLE management.