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Effects of clonal variation on growth, metabolism, and productivity in response to trophic factor stimulation: a study of Chinese hamster ovary cells producing a recombinant monoclonal antibody

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Abstract

The growth, metabolism, and productivity of five Chinese hamster ovary (CHO) clones were explored in response to stimulation with insulin (5 mg/L) and LONG®R3IGF-I (20 μg/L or 100 μg/L). All five clones were derived from the same parental CHO cell line (DG44) and produced the same recombinant monoclonal antibody, with varying specific productivities. There was no uniform response among the clones to stimulation with the different trophic factors. One of the high productivity clones (clone D) exhibited significantly better growth in response to LONG®R3IGF-I; whereas the other clones showed equivalent or slightly better growth in the presence of insulin. Three out of the five clones had higher specific productivities in the presence of insulin (although not statistically significant); one was invariant, and the final clone exhibited slightly higher specific productivity in the presence of LONG®R3IGF-I. Total product titers exhibited moderate variation between culture conditions, again with neither trophic factor being clearly superior. Overall product titers were affected by variations in both integrated viable cell density and specific productivity. Nutrient uptake and metabolite generation patterns varied strongly between clones and much less with culture conditions. These results point to the need for careful clonal analysis when selecting clones, particularly for platform processes where media and culture conditions are predetermined.

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Acknowledgments

The authors would like to thank Drs. Sally Grosvenor, Larissa Chirkova, Anthony Simula, and Geoffrey Francis for advice on experimental design and comments on the manuscript and Dr. Thomas Kiehl, Christian Schenkelberg, and Yong Jun An for technical assistance with the cell counting. This work was supported by Novozymes Biopharma AU.

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  1. Susan T. Sharfstein

    Present address: College of Nanoscale Science and Engineering, University at Albany, NFE, 257 Fuller Road, Albany, NY, 12203, USA

Authors and Affiliations

  1. Biochemistry and Biophysics Program, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY, 12180, USA

    Hussain Dahodwala & Mark Nowey

  2. Application Research and Development, Novozymes Biopharma AU Ltd, 28 Dalgleish St., Thebarton, SA, 5031, Australia

    Tatyana Mitina

  3. Department of Chemical and Biological Engineering, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY, 12180, USA

    Susan T. Sharfstein

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  1. Hussain Dahodwala
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Correspondence to Susan T. Sharfstein.

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Dahodwala, H., Nowey, M., Mitina, T. et al. Effects of clonal variation on growth, metabolism, and productivity in response to trophic factor stimulation: a study of Chinese hamster ovary cells producing a recombinant monoclonal antibody. Cytotechnology 64, 27–41 (2012). https://doi.org/10.1007/s10616-011-9388-z

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