抗体异质性对抗体药物功能和代谢影响的研究进展

Advances of the effects of antibody heterogeneity on the function and metabolism of monoclonal antibody drugs

抗体药物常呈现微观不均一性,即"异质性",包括糖基化、电荷、相对分子质量大小等相关的异构体。这些异构体绝大部分来自于"细胞工厂"对重组蛋白的翻译后修饰作用,如聚体、降解、糖基化修饰、氧化、脱酰基化、二硫键错配等。这些修饰不仅对抗体的质量、安全性和有效性均可能造成影响,而且也是整个抗体生产工艺的重要指征。本文对抗体糖基化、电荷及相对分子质量大小等异质性与药物有效性、安全性、药代动力学及免疫原性等的联系进行综述,有助于进一步认识抗体结构与功能关系,并希望为抗体药物尤其是生物类似药物的开发提供一定的依据和指导。

Antibody drugs often show ＂heterogeneity＂,including the related isomers differing from one another in glycosylation,charge or molecular size.Most of these isomers come from post-translational modifications,such as aggregation,degradation,glycosylation,oxidation,deamidation or disulfide misfolding,of the recombinant protein in the ＂cell factories＂.These modifications not only influence the quality,safety and efficacy of the antibodies,but also serve as an important indication of product quality throughout the whole process of antibody production.This paper reviews the relationship between glycoslation,charge and size heterogeneities of monoclonal antibodies and drug efficacy,safety,pharmacokinetics as well as immunogenicity,contributing to a better understanding of the relationship between antibody structure and function.It will provide some support and guidance for the research and development of antibody drugs,especially biosimilars.