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嵌合抗原受体 T 细胞治疗系统性红斑狼疮:一种有前途的新兴疗法。

CAR-T cells for treating systemic lupus erythematosus: A promising emerging therapy.

机构信息

Department of Clinical Immunology and Internal Medicine, National Reference Center for Systemic Autoimmune Diseases (CNR RESO), Tertiary Center for Primary Immunodeficiency, Strasbourg University Hospital, 67000 Strasbourg, France; University Strasbourg, INSERM UMR - S1109, Institut thématique interdisciplinaire (ITI) de Médecine de Précision de Strasbourg, Transplantex NG, Fédération Hospitalo-Universitaire OMICARE, Fédération de Médecine Translationnelle de Strasbourg (FMTS), 67000 Strasbourg, France.

Department of Clinical Immunology and Internal Medicine, National Reference Center for Systemic Autoimmune Diseases (CNR RESO), Tertiary Center for Primary Immunodeficiency, Strasbourg University Hospital, 67000 Strasbourg, France; University Strasbourg, INSERM UMR - S1109, Institut thématique interdisciplinaire (ITI) de Médecine de Précision de Strasbourg, Transplantex NG, Fédération Hospitalo-Universitaire OMICARE, Fédération de Médecine Translationnelle de Strasbourg (FMTS), 67000 Strasbourg, France.

出版信息

Joint Bone Spine. 2024 Sep;91(5):105702. doi: 10.1016/j.jbspin.2024.105702. Epub 2024 Feb 7.

Abstract

Chimeric Antigen Receptor T-cell therapy (CAR-T), currently employed routinely for treating B-cell malignancies, has emerged as a groundbreaking approach in addressing severe autoimmune diseases, especially for systemic lupus erythematosus (SLE). The immunological rationale for targeting B lymphocytes in autoimmune diseases is well-established, demonstrating success in numerous autoantibody-mediated autoimmune conditions through targeted therapies over several years. However, this approach has often proven ineffective in the context of systemic lupus erythematosus. Recent data on CAR-T usage in lupus, revealed promising results including rapid and prolonged remission without treatment, highlighting the potential of CAR-T therapy in severe lupus cases. This article provides a comprehensive overview of CAR-T cells, tracing their evolution from hematological malignancies to their recent applications in autoimmune disorder, especially in lupus. Clinical trials within a regulated framework are now imperative to assess the procedural aspects in order to validate the considerable promise of CAR-T cell therapy in the field of autoimmune diseases. This includes evaluating safety and long-term efficacy and security of the procedure, the benefit-risk ratio in the field of autoimmunity, the availability and cost-related issues associated with this emerging cellular therapy procedure.

摘要

嵌合抗原受体 T 细胞疗法(CAR-T)目前被常规用于治疗 B 细胞恶性肿瘤,已成为治疗严重自身免疫性疾病(尤其是系统性红斑狼疮[SLE])的突破性方法。针对自身免疫性疾病中的 B 淋巴细胞的免疫原理已经得到充分证实,通过靶向治疗在数年内成功治疗了多种自身抗体介导的自身免疫性疾病。然而,这种方法在系统性红斑狼疮的情况下往往效果不佳。最近关于 CAR-T 在狼疮中的应用的数据显示出了有希望的结果,包括快速和持久的缓解而无需治疗,这突出了 CAR-T 疗法在严重狼疮病例中的潜力。本文全面概述了 CAR-T 细胞,追溯了它们从血液系统恶性肿瘤到最近在自身免疫性疾病中的应用的发展历程,尤其是在狼疮中的应用。现在迫切需要在监管框架内进行临床试验,以评估程序方面,从而验证 CAR-T 细胞疗法在自身免疫性疾病领域的巨大潜力。这包括评估安全性和长期疗效和安全性、该程序在自身免疫领域的获益-风险比、这种新兴细胞疗法程序的可及性和与成本相关的问题。

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