文献类型：期刊文献

英文题名：Biphasic addition strategy of hypoxanthine and thymidine for improving monoclonal antibody production

作者：Chen, Fei[1];Ye, Zhaoyang[1];Zhao, Liang[1];Liu, Xuping[1];Fan, Li[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：2012

卷号：114

期号：3

起止页码：347

外文期刊名：JOURNAL OF BIOSCIENCE AND BIOENGINEERING

收录：;EI(收录号：20123215330115);WOS:【SCI-EXPANDED(收录号:WOS:000309431700018)】；

基金：This work was supported by a grant from the Shanghai University Young Teacher Training Program (No. hlg11011).

语种：英文

外文关键词：Chinese hamster ovary cells; Hypoxanthine; Thymidine; Monoclonal antibody production; Fed-batch culture

摘要：In our previous study, we demonstrated that combinatorial addition of hypoxanthine (10 mg/L) and thymidine (2 mg/L) was able to stimulate initial cell growth and elevate volumetric concentration of antibody by 22% (Chen et al., Appl. Microbiol. Biotechnol., 93, 169-178, 2012). In this study, a systematic study was carried out to investigate the effects of hypoxanthine and thymidine (H&T) on cell growth and antibody production in a much wider range of concentration. In addition, we pursued to establish a highly productive fed-batch culture via rationally designing H&T addition regime. It was found that both cell growth and antibody production in batch cultures were H&T concentration-dependent. Specifically, a low concentration stimulated cell growth while exerting no influence on specific productivity (q(mAb)), and a high concentration inhibited cell growth, however, significantly enhancing q(mAb). Subsequent experiments with fed-batch shaking flasks demonstrated the feasibility of improving antibody production using a biphasic addition strategy for H&T: supplementing a low concentration of H&T during initial cell growth phase and a high concentration of H&T at the production phase. By applying the optimized feeding regime, a maximum viable cell density (VCD) of 6.45 x 10(6) cells/mL and volumetric antibody production of 632 mg/L were achieved in a 2 L-B.Braun bioreactor. Taken together, in this study, a biphasic H&T addition strategy for cell culture was developed, which hold great promise to improve antibody production. (C) 2012, The Society for Biotechnology, Japan. All rights reserved.