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Med (New York, N.Y.). 2025 May 28:100749. doi: 10.1016/j.medj.2025.100749 Q111.82025

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

同种异体CD19靶向CAR-T治疗难治性系统性红斑狼疮获得持续缓解 翻译改进

Dandan Wang  1, Xiaobing Wang  2, Binghe Tan  3, Xin Wen  1, Songying Ye  2, Yingyi Wu  1, Xuan Cao  1, Xin Zhang  1, Chun Wang  1, Linyu Geng  1, Huayong Zhang  1, Xuebing Feng  1, Biao Zheng  4, Yanran He  5, Mingyao Liu  3, Xin Wu  2, Bing Du  6, Lingyun Sun  7, Huji Xu  8

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作者单位

  • 1 Department of Rheumatology and Immunology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China.
  • 2 Department of Rheumatology and Immunology, National Key Laboratory for Immunity and Inflammation, Changzheng Hospital, Naval Medical University, Shanghai, China.
  • 3 Shanghai Frontiers Science Center of Genome Editing and Cell Therapy, Shanghai Key Laboratory of Regulatory Biology and School of Life Sciences, East China Normal University, Shanghai 200241, China; BRL Medicine, Inc., Shanghai, China.
  • 4 BRL Medicine, Inc., Shanghai, China.
  • 5 Committee on Cancer Biology, The University of Chicago, Chicago, IL 60637, USA.
  • 6 Shanghai Frontiers Science Center of Genome Editing and Cell Therapy, Shanghai Key Laboratory of Regulatory Biology and School of Life Sciences, East China Normal University, Shanghai 200241, China; BRL Medicine, Inc., Shanghai, China. Electronic address: bdu@bio.ecnu.edu.cn.
  • 7 Department of Rheumatology and Immunology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China. Electronic address: lingyunsun@nju.edu.cn.
  • 8 Department of Rheumatology and Immunology, National Key Laboratory for Immunity and Inflammation, Changzheng Hospital, Naval Medical University, Shanghai, China; School of Medicine, Tsinghua University, Beijing 100084, China; Peking-Tsinghua Center for Life Sciences, Tsinghua University, Beijing 100084, China. Electronic address: xuhuji@smmu.edu.cn.

    • DOI: 10.1016/j.medj.2025.100749 PMID: 40446794

    摘要 中英对照阅读

    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.

    Keywords: CAR-T cell; Translation to patients; allogeneic; remission; safety; systemic lupus erythematosus.

    Keywords：CD19-targeted CAR-T therapy; systemic lupus erythematosus; durable remission

    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。本研究旨在评估异基因嵌合抗原受体（CAR-T）细胞疗法对狼疮患者的治疗安全性。该研究已在ClinicalTrials.gov注册（NCT05859997）。

    方法： 本研究纳入了3名难治性和严重的多器官受累SLE患者。从健康供体中基因工程改造的CD19靶向CAR-T细胞以每公斤体重1百万个细胞的剂量通过静脉输注给药。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症（ICANS）的发生情况被评估。同时，还对CAR+ T细胞增殖及外周B细胞数量进行了评价，并基于SELENA-SLEDAI、SLEDAI-2K、BILAG、临床SLE响应指数4（SRI-4）和DORIS缓解指数来评估临床疗效。

    发现： 2023年8月至10月期间，共纳入了3名SLE患者，并完成了为期12个月的随访。未发生GvHD、CRS或ICANS事件，且无严重不良反应记录。CAR+ T细胞在体内扩增，在第14天达到峰值后逐渐减少。淋巴细胞中B细胞的比例和绝对循环B细胞计数显著降低。患者1因无法解决的严重血小板减少症及需要添加免疫抑制剂而于第一个月退出研究。SELENA-SLEDAI和SLEDAI-2K评分下降，所有患者在最后一次访问时均达到了SRI-4缓解。

    结论： 对于严重且难治性的SLE患者，异基因CAR-T细胞治疗表现出显著的安全性和疾病缓解的临床疗效。

    资助： 82320108010, 31821003, 81930043, 82330055 和 U24A20380.

    关键词： CAR-T细胞；转化到患者治疗；异基因；缓解；安全性；系统性红斑狼疮。

    关键词：CD19靶向CAR-T疗法; 系统性红斑狼疮; 持久缓解

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    ISSN：2666-6340

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    IF/分区：11.8/Q1

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