细胞培养过程对单克隆抗体糖基化修饰的影响和调控

doi:10.13523/j.cb.20190813

中国生物工程杂志

2019, Vol. 39

Issue (8): 95-103 DOI: 10.13523/j.cb.20190813

综述

细胞培养过程对单克隆抗体糖基化修饰的影响和调控

江一帆¹,贾宇¹,王龙²,王志明^1,^*(

)

1 华北制药新药研究开发有限责任公司抗体药物研究国家重点实验室石家庄 050015
2 上海多宁生物科技有限公司上海 201619

The Glycosylation Design and Control of Monoclonal Antibody by Cell Culture

JIANG Yi-fan¹,JIA Yu¹,Wang Long²,WANG Zhi-ming^1,^*(

)

1 New Drug Research and Development Company Limited, North China Pharmaceutical Corporation, State Key Laboratory of Antibody Drug Development, Shijiazhuang 050015, China
2 Shanghai Duoning Biotechnology Co. Ltd., Shanghai 201619, China

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摘要：

在单克隆抗体药生产过程中,其糖基化修饰可能受到多种工艺参数的影响,因而容易产生异质性,并且抗体糖基化和抗体半衰期、免疫源性、ADCC、CDC等密切相关,所以单克隆抗体的糖基化修饰是重要的质量属性,需要在生物药尤其是生物类似药开发过程中重点关注,并加以调控。通过概述培养过程中的细胞株、培养工艺,以及培养基对糖型的影响,讨论如何在工艺开发过程开展研究,确保产品糖基化的一致性,从而保证单抗药物的疗效及安全性。

关键词： 单克隆抗体; 糖基化修饰; 培养工艺

Abstract:

In monoclonal antibody drug production process, its glycosylation modification may be affected by a variety of process parameters, therefore come into being heterogeneity easily, and Antibody glycosylation is closely related to antibody half-life, immunogenicity, ADCC, CDC, and so on, so glycosylation is an important quality index for monoclonal antibody drugs, It is necessary to pay attention to and regulate the development of biological drugs, especially in the development of biosimilar. This paper strengthens the understanding of stable and consistent glycosylation by discussing the influence of various important control indicators in the culture process, such as pH, DO, osmolarity and temperature, to guide the efficacy and safety of monoclonal antibody drugs.

Key words: Monoclonal antibody Glycosylation Culture process

收稿日期: 2019-01-03 出版日期: 2019-09-18

ZTFLH:

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通讯作者: 王志明 E-mail: wzm3994@163.com

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引用本文:

江一帆,贾宇,王龙,王志明. 细胞培养过程对单克隆抗体糖基化修饰的影响和调控[J]. 中国生物工程杂志, 2019, 39(8): 95-103.

JIANG Yi-fan,JIA Yu,Wang Long,WANG Zhi-ming. The Glycosylation Design and Control of Monoclonal Antibody by Cell Culture. China Biotechnology, 2019, 39(8): 95-103.

链接本文:

https://manu60.magtech.com.cn/biotech/CN/10.13523/j.cb.20190813 或 https://manu60.magtech.com.cn/biotech/CN/Y2019/V39/I8/95

图1 抗体糖基化合成[5]

图2 工程细胞株表达抗体常见N-糖基化类型[4]

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