Engineering therapeutic antibodies targeting G-protein-coupled receptors.
Engineering therapeutic antibodies targeting G-protein-coupled receptors.
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DOI：
10.1038/emm.2015.105
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发表时间：
2016-02-05
影响因子：
12.8
通讯作者：
Jung ST
中科院分区：
文献类型：
--
作者：
Jo M;Jung ST
G蛋白偶联受体（GPCR）是最具吸引力的治疗靶标类别之一，因为它们在细胞内信号传导中发挥着关键作用，并且与多种疾病（包括癌症、感染和炎症）具有临床相关性。然而，高构象变异性、胞外表位暴露面积小以及GPCR抗原制备困难等问题阻碍了治疗性抗GPCR抗体的分离以及GPCR结构、功能和生化机制的研究。为了克服产生具有增强功效和安全性的高特异性抗GPCR抗体的挑战，基于实验动物免疫和高通量定向进化的新兴系统已成功设计并使用各种形式的抗原进行筛选。
G-protein–coupled receptors (GPCRs) are one of the most attractive therapeutic target classes because of their critical roles in intracellular signaling and their clinical relevance to a variety of diseases, including cancer, infection and inflammation. However, high conformational variability, the small exposed area of extracellular epitopes and difficulty in the preparation of GPCR antigens have delayed both the isolation of therapeutic anti-GPCR antibodies as well as studies on the structure, function and biochemical mechanisms of GPCRs. To overcome the challenges in generating highly specific anti-GPCR antibodies with enhanced efficacy and safety, various forms of antigens have been successfully designed and employed for screening with newly emerged systems based on laboratory animal immunization and high-throughput-directed evolution.