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靶向G蛋白偶联受体和离子通道的功能性单克隆抗体的发现。

Discovery of functional monoclonal antibodies targeting G-protein-coupled receptors and ion channels.

作者信息

Wilkinson Trevor C I

机构信息

Antibody Discovery and Protein Engineering, MedImmune, Milstein Building, Granta Park, Cambridge CB21 6GH, U.K.

出版信息

Biochem Soc Trans. 2016 Jun 15;44(3):831-7. doi: 10.1042/BST20160028.

DOI:10.1042/BST20160028
PMID:27284048
Abstract

The development of recombinant antibody therapeutics is a significant area of growth in the pharmaceutical industry with almost 50 approved monoclonal antibodies on the market in the US and Europe. Despite this growth, however, certain classes of important molecular targets have remained intractable to therapeutic antibodies due to complexity of the target molecules. These complex target molecules include G-protein-coupled receptors and ion channels which represent a large potential target class for therapeutic intervention with monoclonal antibodies. Although these targets have typically been addressed by small molecule approaches, the exquisite specificity of antibodies provides a significant opportunity to provide selective modulation of these target proteins. Given this opportunity, substantial effort has been applied to address the technical challenges of targeting these complex membrane proteins with monoclonal antibodies. In this review recent progress made in the strategies for discovery of functional monoclonal antibodies for these challenging membrane protein targets is addressed.

摘要

重组抗体疗法的发展是制药行业一个重要的增长领域,在美国和欧洲市场上有近50种获批的单克隆抗体。然而,尽管有这种增长,但由于靶分子的复杂性,某些重要的分子靶标类别仍然难以用治疗性抗体攻克。这些复杂的靶分子包括G蛋白偶联受体和离子通道,它们是单克隆抗体进行治疗干预的一个具有巨大潜力的靶标类别。尽管这些靶标通常采用小分子方法来解决,但抗体的高度特异性为选择性调节这些靶蛋白提供了重大机遇。鉴于此机遇,人们已付出大量努力来应对用单克隆抗体靶向这些复杂膜蛋白的技术挑战。在这篇综述中,探讨了针对这些具有挑战性的膜蛋白靶标发现功能性单克隆抗体的策略方面取得的最新进展。

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