CAR T-cell therapy in systemic sclerosis: the next frontier in immune modulation

PURPOSE OF REVIEW: Cellular therapies such as CD19-targeting CAR T cells are a rapidly evolving field in an area of unmet clinical needs: autoimmune diseases including systemic sclerosis (SSc). The aim of this review is to summarize the available data on safety and efficacy of CAR T-cell therapy in SSc and to discuss upcoming developments and challenges for the near future. RECENT FINDINGS: Several case reports and series recently described the treatment of SSc patients with CD19-targeting CAR T cells, which resulted in profound B-cell depletion and downregulation of autoimmunity. Encouraging results on efficacy in several disease manifestations were reported including skin and organ fibrosis. Also, vascular phenomena including digital ulcerations improved. The safety profile showed mostly mild-to-moderate cytokine release syndrome (CRS) and low rates of neurotoxicity. Infectious complications ranged from mild upper airway infections to pneumonia. However, a case of herpes simplex reactivation with secondary lethal haemophagocytosis was also described. SUMMARY: Current evidence suggests very promising effects of CD19-CAR T-cell therapy on several SSc manifestations. Additional larger trials are needed. Current frontiers are patient selection, refining lymphodepletion protocols, and expanding target antigens beyond CD19.