LeanBioPro, Barcelona, Spain.
iMed - Research Institute for Medicines, Faculty of Pharmacy at University of Lisbon, Lisbon, Portugal.
Adv Biochem Eng Biotechnol. 2020;171:55-86. doi: 10.1007/10_2019_116.
Antibody drugs became an increasingly important element of the therapeutic landscape. Their accomplishment has been driven by many unique properties, in particular by their very high specificity and selectivity, in contrast to the off-target liabilities of small molecules (SMs). Antibodies can bring additional functionality to the table with their ability to interact with the immune system, and this can be further manipulated with advances in antibody engineering.The expansion of strategies related to discovery technologies of monoclonal antibodies (mAbs) (phage display, yeast display, ribosome display, bacterial display, mammalian cell surface display, mRNA display, DNA display, transgenic animal, and human B cell derived) opened perspectives for the screening and the selection of therapeutic antibodies for, theoretically, any target from any kind of organism. Moreover, antibody engineering technologies were developed and explored to obtain chosen characteristics of selected leading candidates such as high affinity, low immunogenicity, improved functionality, improved protein production, improved stability, and others. This chapter contains an overview of discovery technologies, mainly display methods and antibody humanization methods for the selection of therapeutic humanized and human mAbs that appeared along the development of these technologies and thereafter. The increasing applications of these technologies will be highlighted in the antibody engineering area (affinity maturation, guided selection to obtain human antibodies) giving promising perspectives for the development of future therapeutics.
抗体药物已成为治疗领域中越来越重要的组成部分。它们的成功主要归因于许多独特的特性，特别是与小分子 (SMs) 的非特异性靶标缺陷相比，它们具有非常高的特异性和选择性。抗体能够与免疫系统相互作用，从而为治疗带来额外的功能，并且通过抗体工程的进步可以进一步操纵这种功能。单克隆抗体 (mAbs) 的发现技术（噬菌体展示、酵母展示、核糖体展示、细菌展示、哺乳动物细胞表面展示、mRNA 展示、DNA 展示、转基因动物和人 B 细胞衍生）相关策略的扩展为筛选和选择治疗性抗体提供了前景，理论上可以针对任何来自任何生物体的目标。此外，还开发和探索了抗体工程技术，以获得所选候选药物的某些特性，如高亲和力、低免疫原性、改善的功能、改善的蛋白生产、提高的稳定性等。本章概述了发现技术，主要是展示方法和抗体人源化方法，用于选择治疗性人源化和人源 mAbs，这些方法随着这些技术的发展而出现，并在此后得到了进一步的应用。将重点介绍这些技术在抗体工程领域的应用（亲和力成熟、引导选择获得人源抗体），为未来治疗药物的开发带来了广阔的前景。
