Work

CAR-T Cell Therapy in Autoimmune Diseases: Promise, Progress, and Pitfalls

Year: 2025

Type: article

Abstract: Background: Chimeric Antigen Receptor T-cell (CAR-T) cell therapy has revolutionized cancer treatment and is now being explored as a novel approach to treat refractory autoimmune diseases by targeting autoreactive immune components, especially B cells. Objective: Our aim was to provide a narrative review of the current evidence, mechanisms, efficacy, safety, and future directions of CAR-T cell therapy in autoimmune diseases. Methods: A structured literature search was conducted in MEDLINE via PubMed using keywords such as “CAR-T”, “chimeric antigen receptor T-cell”, “autoimmune diseases”, “lupus”, “rheumatoid arthritis”, “multiple sclerosis”, and “vasculitis”. Studies on CAR-T mechanisms, efficacy, safety, and clinical outcomes were included. Results: CAR-T cell therapies, especially CD19-directed constructs, demonstrated sustained drug-free remission in all patients across early SLE case series (n = 5–7), with normalization of serological markers and improved renal outcomes. Emerging preclinical and early clinical data in rheumatoid arthritis, multiple sclerosis, ANCA-associated vasculitis, juvenile autoimmune diseases, and idiopathic inflammatory myopathies also report clinical improvement and biomarker normalization. Reported adverse events in autoimmune cohorts were limited to mild cytokine release syndrome in a minority of cases, with no severe neurotoxicity or life-threatening infections, suggesting a more favorable safety profile compared to oncology settings. In parallel, next-generation innovations—including dual-target CARs, CAR-Tregs, and molecular safety switches—are advancing toward clinical translation. Conclusions: CAR-T cell therapy is emerging as a transformative strategy for autoimmune disease management, especially in refractory cases. Although initial outcomes are promising, long-term safety, cost-effectiveness, and broader accessibility remain key challenges. Future research should focus on optimizing cell targets, minimizing off-target effects, and improving affordability.

Source: Rheumato

DOI: 10.3390/rheumato5040015

Authors: Alessandro Conforti, Carlos Cifuentes-González, Alarico Ariani, Alberto Lo Gullo, Rupesh Agrawal