Effect of sodium butyrate on the assembly, charge variants, and galactosylation of antibody produced in recombinant Chinese hamster ovary cells

被引:39
作者
Hong, Jong Kwang [1 ]
Lee, Sang Min [1 ]
Kim, Kyung-Yong [2 ]
Lee, Gyun Min [1 ]
机构
[1] Korea Adv Inst Sci & Technol, Dept Biol Sci, Taejon 305701, South Korea
[2] ISU ABXIS, Global R&D Ctr, Songnam 463400, South Korea
关键词
Antibody; Assembly; Charge heterogeneity; CHO cells; Galactosylation; Sodium butyrate; CHO-CELLS; ENDOPLASMIC-RETICULUM; LIGHT-CHAINS; HUMAN THROMBOPOIETIN; CULTURE-CONDITIONS; PROTEIN; IMMUNOGLOBULIN; HETEROGENEITY; GLYCOSYLATION; APOPTOSIS;
D O I
10.1007/s00253-014-5596-8
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Sodium butyrate (NaBu) is known to increase the specific productivity of recombinant Chinese hamster ovary (rCHO) cells. To understand the effects of NaBu on the product quality, rCHO cells producing monoclonal antibody (Mab) were cultivated at various concentrations of NaBu (0 to 4 mM). NaBu increased correctly assembled Mab. In the absence of NaBu, the proportions of intact Mab (2H2L) and heavy chain dimer (2H) were 81 and 15 %. At 1 mM NaBu, the proportion of 2H2L increased to 93 %, whereas the proportion of 2H decreased to 2 %. No further increase in the proportion of 2H2L was obtained at a higher NaBu concentration. NaBu also affected the charge heterogeneity of Mab, which may affect the efficacy of Mab. The basic charge variants of Mabs increased with an increase in the NaBu concentration. In addition, NaBu affected the galactosylation of Mab negatively. Overall, the data obtained here show that NaBu used in rCHO cell cultures for improved Mab production affects certain quality aspects of Mab, in this case, the charge heterogeneity and galactosylation.
引用
收藏
页码:5417 / 5425
页数:9
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