Chimeric antigen receptor t-cell therapy for systemic autoimmune diseases: a systematic review

Background

Systemic autoimmune diseases pose significant therapeutic challenges due to suboptimal responses and frequent relapses with conventional treatments. Chimeric Antigen Receptor (CAR) T-cell therapy has emerged as a transformative approach, offering targeted, sustained B-cell depletion. This review evaluates its efficacy and safety in refractory systemic autoimmune conditions.

Methods

A literature search was conducted across PubMed, Scopus, and Web of Science for studies published in recent years. Eligible studies included clinical trials, observational studies, and case series assessing CAR T-cell therapy in treatment-resistant patients. Study selection and data extraction followed systematic protocols; quality was appraised using risk-of-bias tools. A narrative synthesis was performed due to heterogeneity.

Results

Emerging evidence suggests CAR T-cell therapy is associated with rapid, sustained clinical remission in severe, refractory cases, particularly Systemic Lupus Erythematosus. Consistent findings include profound B-cell depletion and significant reductions in autoantibody titres. However, the evidence base is limited by small sample sizes, short follow-up, and variable treatment protocols. Reported adverse events, including cytokine-mediated inflammatory responses and infection risk, were generally manageable but represent important safety considerations.

Conclusions

CAR T-cell therapy demonstrates promise as a novel therapeutic strategy for refractory autoimmune diseases, with the potential to redefine treatment paradigms. However, current evidence remains preliminary. Robust, large-scale studies with long-term follow-up are essential to establish safety, durability, and generalizability in broader clinical practice.

Key messages

• CAR T-cell therapy shows promise for rapid and sustained remission in severe, refractory autoimmune diseases like systemic lupus erythematosus.

• While promising, current evidence is limited by small samples and short follow-ups; large-scale studies are essential for clinical practice.