文献类型：期刊文献

英文题名：Investigation into the impact of tyrosine on the product formation and quality attributes of mAbs in rCHO cell cultures

作者：Zhang, Weijian[1];Liu, Xuping[1];Tang, Hongping[1];Zhang, Xinran[1];Zhou, Yanan[1];Fan, Li[1];Wang, Haibin[2];Tan, Wen-Song[1];Zhao, Liang[1]

机构：[1]East China Univ Sci & Technol, State Key Lab Bioreactor Engn, 130 Meilong Rd,POB 309, Shanghai 200237, Peoples R China;[2]Zhejiang Hisun Pharmaceut Co Ltd, Hangzhou 311404, Zhejiang, Peoples R China

年份：2020

卷号：104

期号：16

起止页码：6953

外文期刊名：APPLIED MICROBIOLOGY AND BIOTECHNOLOGY

收录：;EI(收录号：20202608868655);WOS:【SCI-EXPANDED(收录号:WOS:000542502600003)】；

基金：This work was supported by the Fundamental Research Funds for the Central Universities (No. 22221818014).

语种：英文

外文关键词：Chinese hamster ovary cells; Tyrosine; Fed-batch cultures; Critical quality attribute; CD20; Monoclonal antibody

摘要：Tyrosine (Tyr) is crucial to the maintenance of the monoclonal antibody (mAb) titers and quality attributes in fed-batch cultures of recombinant Chinese hamster ovary (rCHO) cells. However, the relation between tyrosine and these aspects is not yet fully defined. In order to further elucidate such a relation, two groups of fed-batch experiments with high tyrosine (H-T) or low tyrosine (L-T) additions producing an IgG1 monoclonal antibody against CD20 were implemented to investigate the intracellular and extracellular effects of tyrosine on the culture performance. It was found that the scarcity of tyrosine led to the distinctive reduction in both viable cell density and antibody specific production rate, hence the sharply reduced titer, possibly related to the impaired translation efficiency caused by the substrate limitation of tyrosine. In addition, alterations to the critical quality attributes were detected in the L-T group, compared to those in the H-T condition. Notable decrease in the contents of intact antibody was found under the L-T condition because of the elevated reductive level in the supernatant. Moreover, the aggregate content in the L-T condition was also reduced, probably resulting from the accumulation of extracellular cystine. In particular, the lysine variant content noticeably increased with tyrosine limitation owing to the downregulation of two carboxypeptidases, i.e., CpB and CpH. Overall, understanding the role of tyrosine in these aspects is fundamental to the increase of product titers and control of critical quality attributes in the monoclonal antibody production of rCHO cell fed-batch cultures.