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[非系统性红斑狼疮结缔组织病患者接受CD19嵌合抗原受体T细胞疗法后的经验]

[Experiences after CD19-CAR T-cell therapy in non-SLE connective tissue diseases].

作者信息

Merkt Wolfgang, Henes Jörg, Bergmann Christina, Lorenz Hanns-Martin

机构信息

Medizinische Klinik V für Hämatologie, Onkologie und Rheumatologie, Sektion Rheumatologie, Universitätsklinikum Heidelberg, INF 410, 69120, Heidelberg, Deutschland.

Klinik für Rheumatologie, Universitätsklinikum Düsseldorf, Düsseldorf, Deutschland.

出版信息

Z Rheumatol. 2025 Sep 1. doi: 10.1007/s00393-025-01700-5.


DOI:10.1007/s00393-025-01700-5
PMID:40888840
Abstract

The treatment of fibrosing autoimmune diseases has so far shown no significant progress with respect to fibrosis. The reason for this is unclear. As in vitro and in vivo data have shown that B‑lymphocytes are not only responsible for autoantibody production but also play an important role in the activation of fibroblasts in an inflammatory event, depletion of B cells is meaningful in these fibrosing autoimmune diseases. The use of the CD20 antibody rituximab has shown some therapeutic benefits but could not decisively improve fibrosis, the prognosis-relevant complication in these diseases. This could be due to the insufficient tissue access of a soluble antibody and the resulting limited depletion of B‑lymphocytes in the inflammatory area of connective tissue. This is the decisive advantage of a cell-mediated destruction of autoimmune cells, which is possible via autologous B‑cell-directed chimeric antigen receptor (CAR) T‑cell therapy. The first data on the treatment of non-SLE connective tissue diseases with fibrosing aspects with autologous CAR T‑cells are developed based on this idea. This overview summarizes and discusses these data. It is important to coordinate research aspects of these experimental treatment approaches and the most important open questions, in our opinion, are proposed at the end of the review.

摘要

迄今为止,在纤维化方面,纤维化自身免疫性疾病的治疗尚未取得显著进展。其原因尚不清楚。由于体外和体内数据表明,B淋巴细胞不仅负责自身抗体的产生,而且在炎症事件中对成纤维细胞的激活也起着重要作用,因此在这些纤维化自身免疫性疾病中,B细胞的清除具有重要意义。使用CD20抗体利妥昔单抗已显示出一些治疗益处,但未能决定性地改善纤维化,而纤维化是这些疾病中与预后相关的并发症。这可能是由于可溶性抗体对组织的 access 不足以及由此导致的结缔组织炎症区域B淋巴细胞的清除受限。这就是细胞介导的自身免疫细胞破坏的决定性优势,这可以通过自体B细胞导向的嵌合抗原受体(CAR)T细胞疗法实现。基于这一理念,首次开展了关于用自体CAR T细胞治疗具有纤维化特征的非SLE结缔组织疾病的数据研究。本综述总结并讨论了这些数据。我们认为,协调这些实验性治疗方法的研究方面非常重要,并且在综述末尾提出了最重要的悬而未决的问题。

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[Experiences after CD19-CAR T-cell therapy in non-SLE connective tissue diseases].

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本文引用的文献

[1]
Persisting CD19.CAR-T cells in combination with nintedanib: clinical response in a patient with systemic sclerosis-associated pulmonary fibrosis after 2 years.

Lancet Respir Med. 2025-7

[2]
BCMA CAR T cells in a patient with relapsing idiopathic inflammatory myositis after initial and repeat therapy with CD19 CAR T cells.

Nat Med. 2025-4-17

[3]
CD19-CAR T-cell therapy induces deep tissue depletion of B cells.

Ann Rheum Dis. 2025-1

[4]
Immunological effects of CD19.CAR-T cell therapy in systemic sclerosis: an extended case study.

Arthritis Res Ther. 2024-12-13

[5]
CD19-targeting CAR T-cell therapy in patients with diffuse systemic sclerosis: a case series.

Lancet Rheumatol. 2025-2

[6]
Rituximab Treatment in Adult Patients With Idiopathic Inflammatory Myositis: A Systematic Review and Meta-analysis.

J Clin Rheumatol. 2025-1-1

[7]
Recent Updates on the Pathogenesis of Inflammatory Myopathies.

Curr Rheumatol Rep. 2024-12

[8]
Case study of CD19 CAR T therapy in a subject with immune-mediate necrotizing myopathy treated in the RESET-Myositis phase I/II trial.

Mol Ther. 2024-11-6

[9]
Allogeneic CD19-targeted CAR-T therapy in patients with severe myositis and systemic sclerosis.

Cell. 2024-9-5

[10]
Autologous CD19-Targeting CAR T Cells in a Patient With Refractory Juvenile Dermatomyositis.

Arthritis Rheumatol. 2024-10

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