The role and potential of CD19-targeted chimeric antigen receptor T-cell therapy in systemic sclerosis

Introduction: Systemic sclerosis (SSc) remains a challenge due to high mortality and resistance to treatment. Chimeric antigen receptor T-cell (CAR-T) technology (anti-CD19) may offer an opportunity for an immune system reset and long-term disease remission, eliminating the need for lifelong medication. Material and methods: This narrative review is based on a literature search in the PubMed and Scopus databases from 2023 to 2026. The main search phrases were: "CAR-T in systemic sclerosis", "CAR-T scleroderma", and "CAR-T SSc." Results: CD19-targeted CAR-T therapy led to significant clinical improvement across analyzed cases. The median modified Rodnan skin score decreased by 8-13 points within 3-6 months. Disease activity, measured by the European Scleroderma Trials and Research Group Activity Index (EUSTAR-AI), showed a mean improvement ranging from 2.1 to 4.2 points. Pulmonary function remained stable or improved, with forced vital capacity increasing by up to 7% in responders. The safety profile was manageable, primarily consisting of grade 1 cytokine release syndrome in approximately 75-80% of patients. Conclusions: CD19-targeted CAR-T therapy is a promising investigational option for patients with refractory SSc. Limitations include small study groups and a lack of randomized controlled trials, warranting further validation in ongoing clinical studies.