Rationale for and clinical development of anti-fractalkine antibody in rheumatic diseases
Rationale for and clinical development of anti-fractalkine antibody in rheumatic diseases
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DOI：
10.1080/14712598.2020.1764931
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发表时间：
2020-05
影响因子：
4.6
通讯作者：
S. Muraoka;J. Nishio;Y. Kuboi;T. Imai;T. Nanki
中科院分区：
文献类型：
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作者：
S. Muraoka;J. Nishio;Y. Kuboi;T. Imai;T. Nanki
摘要引言：风湿性疾病是通过多种免疫细胞亚群损害靶器官的炎性疾病。Fractalkine（FKN）作为化学引诱物以及粘附分子。它通过多种机制参与类风湿性关节炎（RA）和其他风湿性疾病的发病机制：单核细胞和细胞毒性效应T细胞的迁移、成纤维细胞样滑膜细胞的增殖和活化、血管生成和破骨细胞生成。FKN具有作为新的治疗靶点的潜力，抗FKN单克隆抗体用于RA的临床试验正在进行中。已经开发了FKN靶向治疗，并且目前正在2期临床试验中测试人源化抗FKN单克隆抗体。涵盖的领域：本综述总结了FKN参与RA和其他风湿性疾病，包括系统性红斑狼疮（SLE），系统性硬化症，炎性肌炎，干燥综合征（SS），骨关节炎和系统性血管炎的积累证据。专家意见：抗FKN的I/IIa期临床试验证明了其安全性、耐受性和临床疗效。抗FKN治疗在治疗动脉粥样硬化和与RA相关的间质性肺病方面具有潜力。根据最近的研究结果，其他风湿性疾病，包括SLE，多发性肌炎/皮肌炎和SS，也可以使用抗FKN治疗。
ABSTRACT Introduction: Rheumatic diseases are inflammatory diseases that damage target organs via multiple subsets of immune cells. Fractalkine (FKN) acts as chemoattractant as well as adhesion molecule. It contributes to the pathogenesis of rheumatoid arthritis (RA) and other rheumatic diseases through multiple mechanisms: the migration of monocytes and cytotoxic effector T cells, the proliferation and activation of fibroblast-like synoviocytes, angiogenesis, and osteoclastogenesis. FKN has potential as a new therapeutic target, and clinical trials on anti-FKN monoclonal antibodies for RA are ongoing. FKN-targeted therapy has been developed and a humanized anti-FKN monoclonal antibody is currently being tested in phase 2 clinical trials. Areas covered: This review summarizes accumulated evidence on the involvement of FKN in RA and other rheumatic diseases, including systemic lupus erythematosus (SLE), systemic sclerosis, inflammatory myositis, Sjögren’s syndrome (SS), osteoarthritis, and systemic vasculitis. Expert opinion: A phase 1/2a clinical trial on anti-FKN demonstrated its safety, tolerability, and clinical efficacy. Anti-FKN therapy has potential in the treatment of atherosclerosis and interstitial lung diseases associated with RA. Based on recent findings, other rheumatic diseases, including SLE, polymyositis/dermatomyositis, and SS, may also be treated using anti-FKN therapy.