CAR T-Cell Therapy in Systemic Lupus Erythematosus: Mechanistic Rationale, Early Clinical Experience, and Future Challenges

Abstract

Systemic lupus erythematosus (SLE) remains a challenging multisystem autoimmune disease characterised by relapses and remissions, often necessitating lifelong immunosuppression. Over the past decades, the therapeutic landscape has evolved from broad-spectrum agents such as cyclophosphamide to more targeted biologics including rituximab, belimumab, and anifrolumab—each contributing to incremental improvements in disease control. More recently, cell-based therapies have emerged as a novel strategy to reprogramme immune responses, including haematopoietic stem cell transplantation, bispecific T-cell engager (BiTE) therapy, and chimeric antigen receptor (CAR) T-cell therapy. CAR T-cell therapy represents a potentially transformative approach in SLE, offering the prospect of sustained clinical and immunological remission without ongoing immunosuppression. In this narrative review, we searched the Medline/PubMed, Scopus, Web of Science, and Directory of Open Access Journals (DOAJ) and included relevant original articles, clinical trials, randomised controlled trials, case studies and case reports published in the last 7 years. In this review, we discuss the mechanistic rationale for CAR T-cell therapy in SLE, review the clinical outcomes reported to date, and explore its promise in ushering a new era of durable, drug-free remission in autoimmune disease.