Nature Medicine：浙江大学黄河团队利用双重靶向CAR-T细胞，成功治疗系统性红斑狼疮

Core Viewpoint - The article discusses the promising results of a phase 1 clinical trial combining CD19-targeting and BCMA-targeting CAR-T cell therapies for treatment-refractory systemic lupus erythematosus (rSLE), highlighting its safety and potential clinical efficacy [2][3][8]. Group 1: Clinical Trial Overview - A phase 1 clinical trial was conducted to evaluate the co-infusion of CD19-targeting and BCMA-targeting CAR-T cells in rSLE patients, showing good safety and promising clinical efficacy [3][8]. - The trial involved 15 patients (14 females and 1 male) who had previously undergone lymphocyte-depleting therapy [6]. Group 2: Safety and Efficacy Results - During a median follow-up of 712 days, no dose-limiting toxicities were observed, with 86.7% of patients experiencing grade 1 cytokine release syndrome, and no neurotoxicity or treatment-related deaths reported [7]. - By week 12, 80% of patients achieved low disease activity status (LLDAS) and DORIS remission criteria, indicating significant improvement in immune homeostasis [9]. Group 3: Mechanistic Insights - The study identified that CD19⁺ B cells and CD19⁻ BCMA⁺ long-lived plasma cells were the main sources of autoantibodies in rSLE patients, supporting the rationale for dual-targeting therapy [6]. - Multi-omics analysis confirmed the elimination of autoreactive CD19⁺ BCMA⁺ clones and the restoration of initial IgM/IgD B cells, suggesting a durable downregulation of interferon-stimulated and BAFF-dependent features [9].