Protein-free fed-batch culture of non-GS NS0 cell lines for production of recombinant antibodies
Article first published online: 24 AUG 2006
Copyright © 2006 Wiley Periodicals, Inc.
Biotechnology and Bioengineering
Volume 96, Issue 2, pages 281–293, 1 February 2007
How to Cite
Burky, J. E., Wesson, M. C., Young, A., Farnsworth, S., Dionne, B., Zhu, Y., Hartman, T. E., Qu, L., Zhou, W. and Sauer, P. W. (2007), Protein-free fed-batch culture of non-GS NS0 cell lines for production of recombinant antibodies. Biotechnol. Bioeng., 96: 281–293. doi: 10.1002/bit.21060
- Issue published online: 23 DEC 2006
- Article first published online: 24 AUG 2006
- Manuscript Accepted: 1 JUN 2006
- Manuscript Received: 16 DEC 2005
- NS0 host cell line;
- fed-batch culture process platform;
- humanized antibodies;
- lactate consumption
Presented is a novel antibody production platform based on the fed-batch culture of recombinant, NS0-derived cell lines. A standardized fed-batch cell culture process was developed for five non-GS NS0 cell lines using enriched and optimized protein-free, cholesterol-free, and chemically defined basal and feed media. The process performed reproducibly and scaled faithfully from the 2-L to the 100-L bioreactor scale achieving a volumetric productivity of > 120 mg/L per day. Fed-batch cultures for all five cell lines exhibited significant lactate consumption when the cells entered the stationary or death phase. Peak and final lactate concentrations were low relative to a previously developed fed-batch process (FBP). Such low lactate production and high lactate consumption rates were unanticipated considering the fed-batch culture basal medium has an unconventionally high initial glucose concentration of 15 g/L, and an overall glucose consumption in excess of 17 g/L. The potential of this process platform was further demonstrated through additional media optimization, which has resulted in a final antibody concentration of 2.64 ± 0.19 g/L and volumetric productivity of > 200 mg/L per day in a 13-day FBP for one of the five production cell lines. Use of this standardized protein-free, cholesterol-free NS0 FBP platform enables consistency in development time and cost effectiveness for manufacturing of therapeutic antibodies. Biotechnol. Bioeng. 2007;96: 281–293. © 2006 Wiley Periodicals, Inc.