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

Abstract

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. 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.” 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. 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.