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Correlation of antibody production rate with glucose and lactate metabolism in Chinese hamster ovary cells

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Abstract

A linear relationship was found between the antibody production rate (q mAb) and the glucose and lactate consumption rate (q GL) in Chinese hamster ovary cells. Under a series of q mAb-perturbing conditions, q GL was determined and a linear relationship between q mAb and q GL was further established (R 2 = 0.914). Mitochondrial dehydrogenase activity was monitored in all the q mAb-perturbing conditions and showed a linear correlation with q GL (R 2 = 0.874) as well as with q mAb. Taken collectively, our results establish that the metabolic parameter, q GL, is linearly correlated with q mAb; this finding strengthens our current understanding of process optimization for antibody production.

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References

  • Bi JX, Shuttleworth J, Al-Rubeai M (2004) Uncoupling of cell growth and proliferation results in enhancement of productivity in p21CIP1-arrested CHO cells. Biotechnol Bioeng 85:741–749

    Article  PubMed  CAS  Google Scholar 

  • Chen K, Liu Q, Xie L, Sharp PA, Wang DIC (2001) Engineering of a mammalian cell line for reduction of lactate formation and high monoclonal antibody production. Biotechnol Bioeng 72:55–61

    Article  PubMed  CAS  Google Scholar 

  • Chen F, Fan L, Wang J, Zhou Y, Ye Z, Zhao L, Tan WS (2011) Insight into the roles of hypoxanthine and thymidine on cultivating antibody-producing CHO cells: cell growth, antibody production and long-term stability. Appl Microbiol Biotechnol doi:10.1007/s00253-011-3484-z

  • Fan L, Zhao L, Ye Z, Sun Y, Kou T, Zhou Y, Tan WS (2010) Effect of culture temperature on TNFC-Fc productivity in recombinant glutamine synthetase-chineses hamster ovary cells. Biotechnol Lett 32:1239–1244

    Article  PubMed  CAS  Google Scholar 

  • Gambhir A, Korke R, Lee J, Fu PC, Europa A, Hu WS (2003) Analysis of cellular metabolism of hybridoma cells at distinct physiological states. J Biosci Bioeng 95:317–327

    PubMed  CAS  Google Scholar 

  • Hinterkörner G, Brugger G, Müller D, Hesse F, Kunert R, Katinger H, Borth N (2007) Improvement of the energy metabolism of recombinant CHO cells by cell sorting for reduced mitochondrial membrane potential. J Biotechnol 129:651–657

    Article  PubMed  Google Scholar 

  • Irani N, Beccaria AJ, Wagner R (2002) Expression of recombinant of recombinant cytoplasmic yeast pyruvate carboxylase for the improvement of the production of human erythropoietin by recombinant BHK-21 cell. J Biotechnol 93:269–282

    Article  PubMed  CAS  Google Scholar 

  • Jiang Z, Sharfstein ST (2008) Sodium butyrate stimulates monoclonal antibody over-expressing in CHO cells by improving gene accessibility. Biotechnol Bioeng 100:189–194

    Article  PubMed  CAS  Google Scholar 

  • Khoo SHG, Al-Rubeai M (2009) Detailed understanding of enhanced specific antibody productivity in NS0 myeloma cells. Biotechnol Bioeng 102:188–199

    Article  PubMed  CAS  Google Scholar 

  • Lee MS, Kim KW, Kim YH, Lee GM (2003) Proteome analysis of antibody-expressing CHO cells in response to hyperosmotic pressure. Biotechnol Prog 19:1734–1741

    Article  PubMed  CAS  Google Scholar 

  • Lin J, Takagi M, Qu Y, Gao P, Yoshida T (1999) Metabolic flux change in hybridoma cells under high osmotic pressure. J Biosci Bioeng 87:255–257

    Article  PubMed  CAS  Google Scholar 

  • Ling WLW, Deng L, Lepore J, Cutler C, Cannon-Carlson S, Wang Y, Voloch M (2003) Improvement of monoclonal antibody production in hybridoma cells by dimethyl sulfoxide. Biotechnol Prog 19:158–162

    Article  PubMed  CAS  Google Scholar 

  • Ma N, Ellet J, Okediadi C, Hermes P, McCormick E, Casnocha S (2009) A single nutrient feed supports both chemically defined NS0 and CHO fed-batch processes: improved productivity and lactate metabolism. Biotechnol Bioeng 25:1353–1363

    Google Scholar 

  • Marchant RJ, Al-Fageeh MB, Underhill MF, Racher AJ, Smales CM (2008) Metabolic rates, growth phase, and mRNA levels influence cell-specific antibody production levels from in vitro-cultured mammalian cells at sub-physiological temperatures. Mol Biotechnol 39:69–77

    Article  PubMed  CAS  Google Scholar 

  • Mulukutla BC, Khan S, Lange A, Hu WS (2010) Glucose metabolism in mammalian cell culture: new insights for tweaking vintage pathways. Trends Biotechnol 28:476–484

    Article  PubMed  CAS  Google Scholar 

  • Pascoe DE, Arnott D, Papoutsakis ET, Miller WM (2007) Proteome analysis of antibody-producing CHO cell lines with different metabolic profiles. Biotechnol Bioeng 98:391–410

    Article  PubMed  CAS  Google Scholar 

  • Renard JM, Spagnoli R, Mazier C, Salles MF, Mandine E (1987) Evidence that monoclonal antibody production kinetics is related to the integral of viable cells in batch systems. Biotechnol Lett 10:91–96

    Article  Google Scholar 

  • Smales CM, Dinnis DM, Stansfield SH, Alete D, Sage EA, Birch JR, Racher AJ, Marshall CT, James DC (2004) Comparative proteomic analysis of GS-NS0 murine myeloma cell lines with varying recombinant monoclonal antibody production rate. Biotechnol Bioeng 88:474–488

    Article  PubMed  CAS  Google Scholar 

  • Tsao YS, Cardoso AG, Condon RGG, Voloch M, Lio P, Lagos JC, Kearns BG, Liu Z (2005) Monitoring Chinese hamster ovary cell culture by the analysis of glucose and lactate metabolism. J Biotechnol 118:316–327

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

This work was supported by the East China University of Science and Technology (ECUST) Special Research Fund for Outstanding Young Scholars (No. YF0157127).

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Authors and Affiliations

  1. The State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, 130 Meilong Road, Shanghai, 200237, China

    Fei Chen, Zhaoyang Ye, Liang Zhao, Xuping Liu, Li Fan & Wen-Song Tan

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  1. Fei Chen
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  2. Zhaoyang Ye
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  3. Liang Zhao
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  4. Xuping Liu
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  5. Li Fan
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  6. Wen-Song Tan
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Correspondence to Li Fan.

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Chen, F., Ye, Z., Zhao, L. et al. Correlation of antibody production rate with glucose and lactate metabolism in Chinese hamster ovary cells. Biotechnol Lett 34, 425–432 (2012). https://doi.org/10.1007/s10529-011-0798-y

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  • DOI: https://doi.org/10.1007/s10529-011-0798-y

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