Wang Dandan, Wang Xiaobing, Tan Binghe, Wen Xin, Ye Songying, Wu Yingyi, Cao Xuan, Zhang Xin, Wang Chun, Geng Linyu, Zhang Huayong, Feng Xuebing, Zheng Biao, He Yanran, Liu Mingyao, Wu Xin, Du Bing, Sun Lingyun, Xu Huji
Department of Rheumatology and Immunology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China.
Department of Rheumatology and Immunology, National Key Laboratory for Immunity and Inflammation, Changzheng Hospital, Naval Medical University, Shanghai, China.
Med. 2025 May 28:100749. doi: 10.1016/j.medj.2025.100749.
Autoreactive B cells play a key role in the pathogenesis of systemic lupus erythematosus (SLE). The aim of this study is to assess the safety of allogeneic chimeric antigen receptor (CAR)-T cells for patients with lupus. This study was registered at ClinicalTrials.gov (NCT05859997).
In this study, 3 patients with refractory and severe SLE with multi-organ involvement were enrolled. Genetically engineered healthy-donor-derived, CD19-targeting CAR-T cells were infused intravenously at a dose of 1 million cells per kilogram of body weight. The safety indices, including the occurrence of graft-versus-host disease (GvHD), cytokine release syndrome (CRS), and immune effector cell-associated neurotoxicity syndrome (ICANS), were evaluated. The proliferation of CAR+ T cells and the number of peripheral B cells were assessed. The clinical efficacy was also assessed based on the SELENA-SLEDAI, SLEDAI-2K, BILAG, clinical SLE responder index-4 (SRI-4), and DORIS remission index.
Between August 2023 and October 2023, 3 patients with SLE were enrolled and completed a 12-month follow-up. No patient underwent GvHD, CRS, or ICANS, and no severe adverse events were recorded. CAR+ T cells expanded in vivo, peaking at day 14, and then declined. The percentage of B cells in lymphocytes and the absolute circulating B cell counts were profoundly decreased. Patient 1 withdrew from the study at month 1 due to unresolved and severe thrombocytopenia and the need for the addition of an immunosuppressive drug. SELENA-SLEDAI and SLEDAI-2K scores declined, and all the patients reached SRI-4 remission at the last visit.
In patients with severe and refractory SLE, allogeneic CAR-T cell therapy showed profound safety and clinical efficacy for disease remission.
82320108010, 31821003, 81930043, 82330055, and U24A20380.
自身反应性B细胞在系统性红斑狼疮（SLE）的发病机制中起关键作用。本研究旨在评估同种异体嵌合抗原受体（CAR）-T细胞对狼疮患者的安全性。本研究已在ClinicalTrials.gov注册（NCT05859997）。
本研究纳入了3例难治性重症SLE且多器官受累的患者。经基因工程改造的健康供体来源的靶向CD19的CAR-T细胞以每千克体重100万个细胞的剂量静脉输注。评估了安全性指标，包括移植物抗宿主病（GvHD）、细胞因子释放综合征（CRS）和免疫效应细胞相关神经毒性综合征（ICANS）的发生情况。评估了CAR+T细胞的增殖和外周B细胞的数量。还根据SELENA-SLEDAI、SLEDAI-2K、BILAG、临床SLE反应指数-4（SRI-4）和多器官反应性指数（DORIS）缓解指数评估了临床疗效。
2023年8月至2023年10月，3例SLE患者入组并完成了12个月的随访。无患者发生GvHD、CRS或ICANS，未记录到严重不良事件。CAR+T细胞在体内扩增，在第14天达到峰值，然后下降。淋巴细胞中B细胞的百分比和循环B细胞绝对计数显著降低。患者1因血小板减少症未缓解且严重，需要加用免疫抑制药物，于第1个月退出研究。SELENA-SLEDAI和SLEDAI-2K评分下降，所有患者在最后一次随访时均达到SRI-4缓解。
在重症难治性SLE患者中，同种异体CAR-T细胞疗法显示出显著的安全性和疾病缓解的临床疗效。
82320108010、31821003、81930043、82330055和U24A20380。
