文献类型：期刊文献

英文题名：Culture temperature modulates monoclonal antibody charge variation distribution in Chinese hamster ovary cell cultures

作者：Zhang, Xintao[1];Sun, Ya-Ting[1];Tang, Hongping[1];Fan, Li[1];Hu, Dongdong[1];Liu, Jintao[1];Liu, Xuping[1];Tan, Wen-Song[1]

机构：[1]E China Univ Sci & Technol, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China

年份：2015

卷号：37

期号：11

起止页码：2151

外文期刊名：BIOTECHNOLOGY LETTERS

收录：;EI(收录号：20152801019679);WOS:【SCI-EXPANDED(收录号:WOS:000361825200005)】；

基金：This work was supported by the National Natural Science Foundation of China (Nos. 21406066, 21206040), the National High Technology Research and Development Program of China (863 Program) (No. 2012AA02A303), the National Science and Technology Major Project (No. 2013ZX10004003-003-003).

语种：英文

外文关键词：Basic carboxypeptidase; Charge variation; Chinese hamster ovary cells; Culture temperature; Lysine variation; Monoclonal ntibodies; Weak cation exchange chromatography

摘要：To investigate the effect of lowering culture temperature on monoclonal antibody charge variation distribution in Chinese hamster ovary cell cultures. In both batch and fed-batch cultures, lowering the culture temperature decreased the antibody acidic variant levels. The acidic variant levels (defined as variants eluting earlier than the main peak of an antibody during HPLC) at 32 A degrees C were about 10 % lower than those at 37 A degrees C at the end of both batch and fed-batch cultures. Additionally, lowering the culture temperature increased the lysine variant level, which further increased basic variant level. The lysine variant levels at 32 A degrees C were about 8 % (batch culture) and 3 % (fed-batch culture) higher than those at 37 A degrees C at the end of cultures. Real-time PCR results suggests that the decrease in carboxypeptidase B transcription level might be partially responsible for the increased lysine variant level at sub-physiological temperatures. Culture temperature exhibits noticeable impact on antibody charge variation distribution, especially the acidic variants and lysine variants.