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Engineered antibody domains with significantly increased transcytosis and half-life in macaques mediated by FcRn 期刊论文

编号：

161c24d5-79c0-4293-8f29-23f66ecf7995
作者：

Ying, Tianlei(应天雷)^[1,2]Wang, Yanping^[3,4];Feng, Yang^[3];Prabakaran, Ponraj^[3];Gong, Rui^[3,5];Wang, Lili(王丽丽)^[1,2]Crowder, Karalyne^[6];Dimitrov, Dimiter S.^[3];
语种：

English
期刊：

MABS ISSN：1942-0862 2015 年 7 卷 5 期 (922 - 930) ; SEP 3
收录：
关键词：

CH2 FcRn half-life CH3 macaques transcytosis antibody domains
摘要：

Engineered antibody domains (eAds) are promising candidate therapeutics but their half-life is relatively short partly due to weak or absent binding to the neonatal Fc receptor (FcRn). We developed a novel approach to increase the eAd binding to FcRn based on a combination of structure-based design, computational modeling and phage display methodologies. By using this approach, we identified 2 IgG1 CH2-derived eAds fused to a short FcRn-binding motif derived from IgG1 CH3 that exhibited greatly enhanced FcRn binding with strict pH dependency. Importantly, the increased affinity resulted in significantly enhanced FcRn-mediated epithelial transcytosis and prolonged elimination half-life (mean 44.1hours) in cynomolgus macaques. These results demonstrate for the first time that the half-life of isolated eAds can be prolonged (optimized) by increasing their binding to FcRn while maintaining their small size, which has important implications for development of therapeutics, including eAd-drug conjugates with enhanced penetration in solid tissues.
推荐引用方式
GB/T 7714：

Ying Tianlei,Wang Yanping,Feng Yang, et al. Engineered antibody domains with significantly increased transcytosis and half-life in macaques mediated by FcRn [J].MABS,2015,7(5):922-930.
APA：

Ying Tianlei,Wang Yanping,Feng Yang,Prabakaran Ponraj,&Dimitrov Dimiter S..(2015).Engineered antibody domains with significantly increased transcytosis and half-life in macaques mediated by FcRn .MABS,7(5):922-930.
MLA：

Ying Tianlei, et al. "Engineered antibody domains with significantly increased transcytosis and half-life in macaques mediated by FcRn" .MABS 7,5(2015):922-930.

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