整合素αVβ3作为类风湿关节炎及相关风湿性疾病的治疗靶点。
Integrin alpha V beta 3 as a target for treatment of rheumatoid arthritis and related rheumatic diseases.
作者信息
Wilder R L
机构信息
Clinical Development, Medimmune, Inc, 35 W Watkins Mill Road, Gaithersburg, MD 20878, USA.
出版信息
Ann Rheum Dis. 2002 Nov;61 Suppl 2(Suppl 2):ii96-9. doi: 10.1136/ard.61.suppl_2.ii96.
Abstract
A substantial and persuasive body of data now exists that supports the view that integrin alpha V beta 3 plays a critical part in activated macrophage dependent inflammation, osteoclast development, migration, and bone resorption, and inflammatory angiogenesis. All of these processes play an important part in the pathogenesis of rheumatoid arthritis (RA) and related arthropathies. Animal arthritis model data further support these concepts and also suggest that therapeutic antagonism of integrin alpha V beta 3 is worthy of further investigation in RA and related arthropathies. To this end, Vitaxin, also known as MEDI-522, has been developed. Vitaxin is a humanised monoclonal IgG1 antibody that specifically binds a conformational epitope formed by both the integrin alpha V and beta 3 subunits. It blocks the interaction of alpha V beta 3 with various ligands such as osteopontin and vitronectin. Clinical trials with Vitaxin in patients with RA are in progress.
摘要
现在已有大量有说服力的数据支持这样一种观点，即整合素αVβ3在活化巨噬细胞依赖性炎症、破骨细胞发育、迁移和骨吸收以及炎性血管生成中起关键作用。所有这些过程在类风湿性关节炎（RA）及相关关节病的发病机制中都起着重要作用。动物关节炎模型数据进一步支持了这些概念，并且还表明整合素αVβ3的治疗性拮抗作用在RA及相关关节病中值得进一步研究。为此，已研发出Vitaxin，也称为MEDI - 522。Vitaxin是一种人源化单克隆IgG1抗体，它特异性结合由整合素αV和β3亚基形成的构象表位。它阻断αVβ3与各种配体（如骨桥蛋白和玻连蛋白）的相互作用。针对RA患者的Vitaxin临床试验正在进行中。
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