Glycoengineering of Therapeutic Antibodies with Small Molecule Inhibitors.
Glycoengineering of Therapeutic Antibodies with Small Molecule Inhibitors.
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DOI：
10.3390/antib10040044
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发表时间：
2021-11-04
期刊：
影响因子：
--
通讯作者：
Wagner GK
中科院分区：
文献类型：
--
作者：
Li S;McCraw AJ;Gardner RA;Spencer DIR;Karagiannis SN;Wagner GK
单克隆抗体（mAb）是现代医学的基石之一，跨越越来越多的治疗领域。所有治疗性mAb都是糖蛋白，即，它们的多肽链用聚糖装饰，聚糖是结构非常多样的寡糖。这些聚糖的存在、不存在和组成可能对单个mAb的药效学和药代动力学特征产生深远影响。因此，从技术、治疗和监管的角度来看，治疗性mAb的糖工程方法-mAb聚糖结构的操纵和优化-引起了极大的兴趣。在这篇综述中，我们简要介绍了糖基化对构成当前所有临床和实验mAb骨架的五类免疫球蛋白（IgG、IgE、伊加、IgM和IgD）的生物学和药理学功能的影响，包括概述常见的mAb表达系统。我们回顾了使用小分子聚糖生物合成抑制剂进行mAb糖工程的一些例子，我们讨论了这种方法的潜在优势和挑战，并概述了未来的潜在应用。该综述的主要目的是向生物学和生物技术界展示可用于mAb糖工程的不断扩大的化学工具箱。
Monoclonal antibodies (mAbs) are one of the cornerstones of modern medicine, across an increasing range of therapeutic areas. All therapeutic mAbs are glycoproteins, i.e., their polypeptide chain is decorated with glycans, oligosaccharides of extraordinary structural diversity. The presence, absence, and composition of these glycans can have a profound effect on the pharmacodynamic and pharmacokinetic profile of individual mAbs. Approaches for the glycoengineering of therapeutic mAbs—the manipulation and optimisation of mAb glycan structures—are therefore of great interest from a technological, therapeutic, and regulatory perspective. In this review, we provide a brief introduction to the effects of glycosylation on the biological and pharmacological functions of the five classes of immunoglobulins (IgG, IgE, IgA, IgM and IgD) that form the backbone of all current clinical and experimental mAbs, including an overview of common mAb expression systems. We review selected examples for the use of small molecule inhibitors of glycan biosynthesis for mAb glycoengineering, we discuss the potential advantages and challenges of this approach, and we outline potential future applications. The main aim of the review is to showcase the expanding chemical toolbox that is becoming available for mAb glycoengineering to the biology and biotechnology community.
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影响因子：
3.1
作者：
Jiang J;Wagner GK
通讯作者：
Wagner GK
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影响因子：
32.4
作者：
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通讯作者：
Ravetch JV
影响因子：
7
作者：
Chandler, Kevin Brown;Mehta, Nickita;Costello, Catherine E.
通讯作者：
Costello, Catherine E.
影响因子：
3.2
作者：
Gloster TM;Davies GJ
通讯作者：
Davies GJ
影响因子：
4.9
作者：
Burkart, MD;Vincent, SP;Wong, CH
通讯作者：
Wong, CH