An iPSC-derived CD19/BCMA CAR-NK therapy in a patient with systemic sclerosis.

This study reports the first-in-human application of iPSC-derived CD19/BCMA dual-targeting chimeric antigen receptor-natural killer (CAR-NK) cells (QN-139b) in a patient with severe, diffuse cutaneous systemic sclerosis. The allogeneic product was genetically edited for reduced alloreactivity and improved in vivo performance, with no structural chromosomal abnormalities detected. The treatment led to significant B cell depletion with minimal toxicity, similar to CAR T cell therapy. The patient showed marked clinical improvements during the 6-month follow-up, including reduced autoantibodies and reversed fibrosis, which are resistant to conventional treatments. Single-cell analysis of peripheral blood revealed that the treatment shifted B cells toward more naive phenotypes and eliminated pathogenic B cells. Proteomic studies demonstrated suppression of inflammation and fibrosis, enhanced tissue regeneration, and improved angiogenesis. Pathological evaluation confirmed the elimination of infiltrated lymphocytes from affected skin along with restored skin and microvascular structure. These findings suggest QN-139b is a promising immune-modulatory treatment for severe autoimmune diseases.