治疗性抗体的筛选、设计与工程

Selection, design, and engineering of therapeutic antibodies.

作者信息

Presta Leonard G

机构信息

Schering-Plough Biopharma, Pali Alto, CA 94304, USA.

出版信息

J Allergy Clin Immunol. 2005 Oct;116(4):731-6; quiz 737. doi: 10.1016/j.jaci.2005.08.003.

DOI:10.1016/j.jaci.2005.08.003

PMID:16210043

Abstract

mAbs account for an increasing portion of marketed human biological therapeutics. As a consequence, the importance of optimal selection, design, and engineering of these not only has expanded in the past 2 decades but also is now coming into play as a competitive factor. This review delineates the 4 basic areas for optimal therapeutic antibody selection and provides examples of the increasing number of considerations necessary for, and options available for, antibody design. Though some of the advances in antibody technology (eg, antibodies derived from phage-display libraries) have already made it to market, other more recent advances, such as engineering antibodies for enhanced effector functions, may not be far behind, especially given the increasing competition for therapeutic antibodies to the same target (eg, anti-CD20 and anti-TNF-alpha).

摘要

单克隆抗体（mAbs）在已上市的人类生物治疗药物中所占比例日益增加。因此，对这些抗体进行优化选择、设计和工程改造的重要性不仅在过去20年中不断扩大，而且如今已成为一个竞争因素。本综述阐述了优化治疗性抗体选择的4个基本领域，并举例说明了抗体设计所需考虑的因素及可用选项的数量不断增加。尽管抗体技术的一些进展（例如，源自噬菌体展示文库的抗体）已经上市，但其他一些最新进展，如设计具有增强效应功能的抗体，可能也不远了，特别是考虑到针对同一靶点的治疗性抗体竞争日益激烈（例如，抗CD20和抗TNF-α）。