Allogeneic CD19-targeted CAR-T therapy in refractory systemic lupus erythematosus achieved durable remission.

IF 12.8 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Med Pub Date : 2025-05-28 DOI:10.1016/j.medj.2025.100749

Dandan Wang, Xiaobing Wang, Binghe Tan, Xin Wen, Songying Ye, Yingyi Wu, Xuan Cao, Xin Zhang, Chun Wang, Linyu Geng, Huayong Zhang, Xuebing Feng, Biao Zheng, Yanran He, Mingyao Liu, Xin Wu, Bing Du, Lingyun Sun, Huji Xu

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引用次数: 0

Abstract

Background: 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).

Methods: 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.

Findings: 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.

Conclusions: In patients with severe and refractory SLE, allogeneic CAR-T cell therapy showed profound safety and clinical efficacy for disease remission.

Funding: 82320108010, 31821003, 81930043, 82330055, and U24A20380.

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异体cd19靶向CAR-T治疗难治性系统性红斑狼疮获得持久缓解。

背景：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。本研究的目的是评估异体嵌合抗原受体(CAR)-T细胞治疗狼疮患者的安全性。本研究已在ClinicalTrials.gov注册（NCT05859997）。方法：本研究纳入3例难治性严重SLE多器官受累患者。基因工程健康供体来源的靶向cd19的CAR-T细胞以每公斤体重100万个细胞的剂量静脉注射。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。观察CAR+ T细胞的增殖和外周血B细胞的数量。根据SELENA-SLEDAI、SLEDAI-2K、BILAG、临床SLE应答指数-4 （SRI-4）和DORIS缓解指数评估临床疗效。研究结果：在2023年8月至2023年10月期间，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，无严重不良事件记录。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细胞的百分比和绝对循环B细胞计数明显下降。患者1因未解决的严重血小板减少症和需要添加免疫抑制药物而在第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访问时均达到SRI-4缓解。结论：在严重难治性SLE患者中，同种异体CAR-T细胞治疗在疾病缓解方面显示出深刻的安全性和临床疗效。资助项目：82320108010、31821003、81930043、82330055、U24A20380。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Med MEDICINE, RESEARCH & EXPERIMENTAL-

CiteScore

17.70

自引率

0.60%

发文量

102

期刊介绍： Med is a flagship medical journal published monthly by Cell Press, the global publisher of trusted and authoritative science journals including Cell, Cancer Cell, and Cell Reports Medicine. Our mission is to advance clinical research and practice by providing a communication forum for the publication of clinical trial results, innovative observations from longitudinal cohorts, and pioneering discoveries about disease mechanisms. The journal also encourages thought-leadership discussions among biomedical researchers, physicians, and other health scientists and stakeholders. Our goal is to improve health worldwide sustainably and ethically. Med publishes rigorously vetted original research and cutting-edge review and perspective articles on critical health issues globally and regionally. Our research section covers clinical case reports, first-in-human studies, large-scale clinical trials, population-based studies, as well as translational research work with the potential to change the course of medical research and improve clinical practice.