Chimeric Antigen Receptor T-cell therapy in systemic autoimmune rheumatic diseases: current insights and future prospects

Abstract

Chimeric Antigen Receptor (CAR) T-cell therapy, revolutionary in treating hematological malignancies, is emerging as a promising approach for systemic autoimmune rheumatic diseases (SARDs). This review examines the potential of CAR T-cell therapy in treating conditions such as systemic lupus erythematosus (SLE), systemic sclerosis (SSc), and idiopathic inflammatory myopathies (IIMs). The evolution of CAR T cells technology, from first to fifth generation, has enhanced its efficacy and persistence. Early clinical studies in SARDs have shown encouraging results, with some patients achieving drug-free remission. CD19-targeted CAR T cells have demonstrated significant B-cell depletion and clinical improvement in patients with SLE, SSc, and IIMs. Despite promising outcomes, challenges remain, including cytokine release syndrome and the need for careful patient selection. Future directions include exploring dual-targeting CARs, chimeric autoantibody receptors (CAARs), and alternative cell sources like γδ T cells, regulatory T cells, natural killer cells. The integration of CAR-based cell therapy into treatment paradigms of patients with SARDs requires further research to optimize efficacy, mitigate side effects, and identify suitable target biomarkers. While hurdles exist CAR-based cell therapy holds the potential to revolutionize management of patients with SARDs, offering hope for long-term, drug-free remission in these complex autoimmune conditions.