文献类型：期刊文献

英文题名：Uridine modulates monoclonal antibody charge heterogeneity in Chinese hamster ovary cell fed-batch cultures

作者：Niu, Huijie[1];Wang, Jiaqi[1];Liu, Mengjuan[1];Chai, Miaomiao[1];Zhao, Liang[1];Liu, Xuping[1];Fan, Li[1];Tan, Wen-Song[1]

机构：[1]East China Univ Sci & Technol, State Key Lab Bioreactor Engn, 130 Mei Long Rd,POB 309, Shanghai 200237, Peoples R China

年份：2018

卷号：5

期号：1

外文期刊名：BIORESOURCES AND BIOPROCESSING

收录：;EI(收录号：20224513084565);WOS:【SCI-EXPANDED(收录号:WOS:000461106800042)】；

基金：This work was supported by The State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology (ECUST).

语种：英文

外文关键词：Charge heterogeneity; Chinese hamster ovary cells; Medium components; Monoclonal antibody; Uridine

摘要：Background: Charge heterogeneity is one of the most critical quality attributes of antibodies, which has strong influence on drug's biological activity and safety. Finding out the key components that affecting charge variants is of great significance for establishing a competitive culture process. In this study, we first illustrated uridine's great impacts on antibody charge heterogeneity in CHO cell fed-batch cultures. Results: Uridine was beneficial to cell growth and the maintenance of cell viability, which made IVCC increased by 50% and the final titer improved by 64%. However, uridine had great influences on mAb's charge variants. In uridine added cultures, the acidic variant levels were about 9% lower than those in control cultures, while the basic variant levels were about 6% higher than those in control cultures. Further investigation found that the decrease of aggregates and glycated forms were responsible for the reduction of acidic variants. What's more, uridine decreased the lysine variant levels. Conclusions: Uridine's addition to fed-batch promoted cell growth and the final titer, in the meanwhile, uridine decreased the acidic variants dramatically. Therefore, feeding uridine is an efficient way to control the generation of acidic charge variants in up-stream process. These findings provide new ideas and guidance for the control and optimization of antibody charge heterogeneity in culture process developments.