BCMA-targeted CAR T cell therapy can effectively induce disease remission in refractory lupus nephritis

作者：Ziwei Hu, Shaozhe Cai, Yikai Yu, Yu Chen, Bei Wang, Di Wang, Rui Zeng, Xiaofeng He, Guifen Shen, Fei Yu, Zhipeng Zeng, Yuxue Chen, Xiaofang Luo, Ziyun Zhang, Peiling Zhang, Hui Xiong, Lin Bai, Ping Ye, Sheng‐Yan Lin, Jishuai Zhang, Cong Ye, Chunrui Li, Lingli Dong · 发表于：Annals of the Rheumatic Diseases · 年份：2025 · DOI：10.1016/j.ard.2025.06.2128 · 被引用次数：34 · 研究领域：CAR-T cell therapy research、Systemic Lupus Erythematosus Research、T-cell and B-cell Immunology

OBJECTIVES: This study aims to evaluate the safety and efficacy of anti-B cell maturation antigen (BCMA)-targeting chimeric antigen receptor (CAR) T cells in treating refractory lupus nephritis (LN). METHODS: This is an open-label, single-arm clinical trial assessing anti-BCMA CAR T cells in treating refractory LN patients. CAR T cells were infused following lymphodepletion therapy with cyclophosphamide and fludarabine. Patients were regularly followed up, in which clinical assessments were performed and laboratory indices were collected. Repeated renal biopsies and single cell RNA sequencing in certain patients were performed to help evaluate the therapeutic efficacy. The primary endpoints were the safe dosage of single infusion and the occurrence of adverse events, while the secondary endpoints focused on the therapeutic efficacy (eg, changes of Systemic Lupus Erythematosus Disease Activity Index 2000 [SLEDAI-2000]). RESULTS: Seven biopsy-confirmed LN patients were enrolled in this study with a median follow-up of 9 months, whose peripheral B cells were effectively eliminated within the first month postinfusions and restored within 3 months except one patient. Hypogammaglobulinemia was frequently observed in this study. Only one case of grade 1 cytokine release syndrome was noted, and no immune effector cell-associated neurotoxicity syndrome or severe infection was reported. SLEDAI-2K scores decreased from a median of 18 (range 10-22) at baseline to 0 (range 0-4) at the las...