治疗性单克隆抗体常见翻译后修饰变异体的分析策略进展  

Analytical Strategies for Common Post-translational Modification Varients of Therapeutical Monoclonal Antibodies

作　　者：吴霖萍[1,2,3] 汪泓 陈钢[2] 

机构地区：[1]中国医药工业研究总院上海医药工业研究院,上海201203 [2]上海市食品药品检验所,上海201203 [3]中国医药工业研究总院中国医药工业信息中心,上海200040

出　　处：《中国医药工业杂志》2017年第11期1545-1558,共14页Chinese Journal of Pharmaceuticals

基　　金：上海市青年科技英才扬帆计划(15YF1410900)

摘　　要：治疗性单克隆抗体(mAb)因其靶向性、免疫原性小、患者耐受良好等特点,近年来发展迅猛,已成为肿瘤、免疫系统疾病和感染性疾病的重要治疗药物。在mAb的生产过程中,不同的理化因素易产生各种翻译后修饰(post-translational modification,PTM)变异体,如糖基化、氧化、糖化、脱酰胺、异构化及端基环化等,这些PTM可能引起抗体理化性质变化,改变与抗体Fc受体的相互反应,影响与目标抗原的结合活性;一些PTM的发生甚至可能降低抗体稳定性、引起免疫原性等。mAb的PTM与产品的安全性、有效性和稳定性息息相关。基于此,本文就治疗性mAb常见的PTM进行综述,阐述其发生的原因,反应位点,对mAb理化性质、生物活性和稳定性可能产生的影响,以及主要的检测策略,旨在为mAb质量的深入分析提供参考。In recent years, therapeutical monoclonal antibodies （mAbs） have been developing rapidly due to its targetability, low-immunogenicity, and good tolerance. They have become important therapeutic agents for numerous diseases including cancer, autoimmune, and infectious diseases. During the production process, different physical and chemical factors may cause kinds of post-translational modifications （PTMs）, including glycosylation, oxidation, glycation, deamidation, isomerization and terminal cyclization, which may cause the change of physicochemical properties, the alteration of interreactions with the antibody Fc receptors, further greatly affect the binding activities with the target antigens. Some PTMs may even lead to the decline of stability, and raise the immunogenicity. PTMs of therapeutical mAbs are closely connected with the safety, efficacy, and consistency of the products. In this review, we focus on the common PTMs of rnAbs, and summarize their causes, modification sites, the influences on the mAbs＇ physicochemical properties, biological activities, and stabilities, as well as the main analytical strategies, aiming to provide some references for the in-depth quality analysis of therapeutical mAbs.

关 键 词：单克隆抗体 翻译后修饰 分析策略 综述 

分 类 号：Q939.91[生物学—微生物学] Q511