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类风湿关节炎的新兴疗法:聚焦单克隆抗体。

Emerging therapies in rheumatoid arthritis: focus on monoclonal antibodies.

作者信息

Senolt Ladislav

机构信息

Department of Rheumatology, First Faculty of Medicine, Charles University, Institute of Rheumatology, Prague, Czech Republic, 128 50, Czech Republic.

出版信息

F1000Res. 2019 Aug 30;8. doi: 10.12688/f1000research.18688.1. eCollection 2019.

Abstract

Advances in the treatment of rheumatoid arthritis (RA) are attributed to several aspects such as new classification criteria enabling early diagnosis and intensive treatment with the application of treat-to-target principles as well as better understanding of the pathogenesis of RA contributing to the development of targeted therapies. However, reaching remission is still not achieved in most patients with RA, which is one of the driving forces behind the continuous development of novel therapies and the optimization of therapeutic strategies. This review will outline several new therapeutic antibodies modulating anti-inflammatory cytokines interleukin (IL)-2 and IL-10 and pro-inflammatory mediators granulocyte-macrophage colony-stimulating factor, fractalkine, and IL-6 that are in various stages of clinical development as well as the progress in manufacturing biotechnologies contributing to the next generation of antibodies and their potential to expand the therapeutic armamentarium for RA. In addition, the fate of unsuccessful therapies including agents targeting IL-15, the IL-20 family, IL-21, chemokine CXCL10, B-cell activating factor (BAFF), and regulatory T (Treg) cells or a novel concept targeting synovial fibroblasts via cadherin-11 will be discussed.

摘要

类风湿关节炎(RA)治疗方面的进展归因于多个方面,例如新的分类标准有助于早期诊断,并通过应用治疗达标原则进行强化治疗,以及对RA发病机制有了更深入的了解,从而推动了靶向治疗的发展。然而,大多数RA患者仍未实现缓解,这是新型疗法不断发展和治疗策略优化的驱动力之一。本综述将概述几种正在临床开发不同阶段的新型治疗性抗体,它们可调节抗炎细胞因子白细胞介素(IL)-2和IL-10以及促炎介质粒细胞-巨噬细胞集落刺激因子、趋化因子和IL-6,同时还将介绍生物技术制造方面的进展,这些进展有助于开发下一代抗体及其扩大RA治疗手段的潜力。此外,还将讨论包括靶向IL-15、IL-20家族、IL-21、趋化因子CXCL10、B细胞活化因子(BAFF)和调节性T(Treg)细胞的药物等未成功疗法的命运,以及通过钙黏蛋白-11靶向滑膜成纤维细胞的新概念。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/210b/6719675/73809a4877be/f1000research-8-20463-g0000.jpg

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