Fc-fusion proteins and FcRn: structural insights for longer-lasting and more effective therapeutics.
Fc-fusion proteins and FcRn: structural insights for longer-lasting and more effective therapeutics.
复制标题
DOI：
10.3109/07388551.2013.834293
复制
发表时间：
2015-06
影响因子：
9
通讯作者：
Blumberg RS
中科院分区：
文献类型：
--
作者：
Rath T;Baker K;Dumont JA;Peters RT;Jiang H;Qiao SW;Lencer WI;Pierce GF;Blumberg RS
近 350 种基于 IgG 的疗法被批准用于临床或正在开发中，用于治疗许多缺乏足够治疗选择的疾病。其中包括分子工程生物制品，其中包含与各种效应分子（所谓的 Fc 融合蛋白）融合的 IgG Fc 结构域，赋予 IgG 的优势，包括与新生儿 Fc 受体 (FcRn) 结合以促进体内稳定性，以及特定效应功能的治疗益处。 IgG 结构-功能关系的进展和对 FcRn 生物学的了解为以前无法解决的疾病提供了治疗机会。本文讨论了已批准的 Fc 融合疗法、新型 Fc 融合蛋白和正在开发的 FcRn 依赖性递送方法，以及 FcRn-Fc 相互作用的工程如何产生更持久、更有效的疗法。
Nearly 350 IgG-based therapeutics are approved for clinical use or are under development for many diseases lacking adequate treatment options. These include molecularly engineered biologicals comprising the IgG Fc-domain fused to various effector molecules (so-called Fc-fusion proteins) that confer the advantages of IgG, including binding to the neonatal Fc receptor (FcRn) to facilitate in vivo stability, and the therapeutic benefit of the specific effector functions. Advances in IgG structure-function relationships and an understanding of FcRn biology have provided therapeutic opportunities for previously unapproachable diseases. This article discusses approved Fc-fusion therapeutics, novel Fc-fusion proteins and FcRn-dependent delivery approaches in development, and how engineering of the FcRn–Fc interaction can generate longer-lasting and more effective therapeutics.