Georg Schett, Andreas Mackensen, Dimitrios Mougiakakos
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引用次数: 2
摘要
尽管自身免疫性疾病的临床管理取得了巨大进展,但许多患者对目前使用的治疗方法没有反应。自身反应性B细胞在自身免疫性疾病的发病机制中发挥着关键作用,如系统性红斑狼疮、类风湿性关节炎和多发性硬化症。消耗B细胞的单克隆抗体,如利妥昔单抗,在自身免疫性疾病中的治疗效果较差,主要是由于自身反应性B细胞在淋巴器官和炎症组织中的持续存在。通过嵌合抗原受体(CARs)过继转移经工程改造的靶向肿瘤细胞的T细胞已成为B细胞恶性肿瘤的一种有效治疗方式。在过去的两年中,针对CD19抗原的自体CAR T细胞的治疗已被引入自身免疫性疾病的治疗中。CD19 CAR T细胞诱导循环B细胞的快速和持续耗竭,以及难治性系统性红斑狼疮和皮肌炎的完全临床和血清学缓解。在本文中,我们讨论了通过CAR T细胞靶向自身反应性B细胞的进化策略,该策略可能用于自身免疫性疾病的靶向治疗。
Despite the tremendous progress in the clinical management of autoimmune diseases, many patients do not respond to the currently used treatments. Autoreactive B cells play a key role in the pathogenesis of autoimmune diseases, such as systemic lupus erythematosus, rheumatoid arthritis, and multiple sclerosis. B-cell-depleting monoclonal antibodies, such as rituximab, have poor therapeutic efficacy in autoimmune diseases, mainly due to the persistence of autoreactive B cells in lymphatic organs and inflamed tissues. The adoptive transfer of T cells engineered to target tumour cells via chimeric antigen receptors (CARs) has emerged as an effective treatment modality in B-cell malignancies. In the last 2 years treatment with autologous CAR T cells directed against the CD19 antigen has been introduced in therapy of autoimmune disease. CD19 CAR T cells induced a rapid and sustained depletion of circulating B cells, as well as in a complete clinical and serological remission of refractory systemic lupus erythematosus and dermatomyositis. In this paper, we discuss the evolving strategies for targeting autoreactive B cells via CAR T cells, which might be used for targeted therapy in autoimmune diseases.
期刊介绍:
The Lancet is a world-leading source of clinical, public health, and global health knowledge. It was founded in 1823 by Thomas Wakley and has been an independent, international weekly general medical journal since then. The journal has an Impact Factor of 168.9, ranking first among 167 general and internal medicine journals globally. It also has a Scopus CiteScore of 133·2, ranking it second among 830 general medicine journals. The Lancet's mission is to make science widely available to serve and transform society, positively impacting people's lives. Throughout its history, The Lancet has been dedicated to addressing urgent topics, initiating debate, providing context for scientific research, and influencing decision makers worldwide.