Effect of sodium butyrate on the assembly, charge variants, and galactosylation of antibody produced in recombinant Chinese hamster ovary cells
- 910 Downloads
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.
KeywordsAntibody Assembly Charge heterogeneity CHO cells Galactosylation Sodium butyrate
This research was supported in part by the Converging Research Center Program through the NRF funded by the MEST (2009–0082276) and a grant from the Fundamental R&D Program for Technology of World Premier Materials funded by the Ministry of Knowledge Economy, Republic of Korea.
- Hendrick V, Winnepenninckx P, Abdelkafi C, Vandeputte O, Cherlet M, Marique T, Renemann G, Loa A, Kretzmer G, Werenne J (2001) Increased productivity of recombinant tissular plasminogen activator (t-PA) by butyrate and shift of temperature: a cell cycle phases analysis. Cytotechnology 36(1–3):71–83PubMedCentralPubMedCrossRefGoogle Scholar
- Khawli LA, Goswami S, Hutchinson R, Kwong ZW, Yang JH, Wang XD, Yao ZL, Sreedhara A, Cano T, Tesar D, Nijem I, Allison DE, Wong PY, Kao YH, Quan C, Joshi A, Harris RJ, Motchnik P (2010) Charge variants in IgG1 Isolation, characterization, in vitro binding properties and pharmacokinetics in rats. Mabs-Austin 2(6):613–624CrossRefGoogle Scholar
- Louis M, Rosato RR, Brault L, Osbild S, Battaglia E, Yang XH, Grant S, Bagrel D (2004) The histone deacetylase inhibitor sodium butyrate induces breast cancer cell apoptosis through diverse cytotoxic actions including glutathione depletion and oxidative stress. Int J Oncol 25(6):1701–1711PubMedGoogle Scholar