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Metabolite profiling of recombinant CHO cells: Designing tailored feeding regimes that enhance recombinant antibody production

Authors

  • Christopher A. Sellick,

    1. Faculty of Life Sciences, The University of Manchester, Michael Smith Building, Oxford Road, Manchester M13 9PT, UK; telephone: 0161 275 5101; fax: 0161 275 5082
    Current affiliation:
    1. MedImmune, Franklin Building, Granta Park, Cambridge CB21 6GH, UK.
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  • Alexandra S. Croxford,

    1. Faculty of Life Sciences, The University of Manchester, Michael Smith Building, Oxford Road, Manchester M13 9PT, UK; telephone: 0161 275 5101; fax: 0161 275 5082
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  • Arfa R. Maqsood,

    1. Faculty of Life Sciences, The University of Manchester, Michael Smith Building, Oxford Road, Manchester M13 9PT, UK; telephone: 0161 275 5101; fax: 0161 275 5082
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  • Gill Stephens,

    1. The School of Chemical Engineering and Analytical Sciences, Manchester Interdisciplinary Biocentre, The University of Manchester, Manchester, UK
    Current affiliation:
    1. Department of Chemical and Environmental Engineering, Process and Environmental Research Division, University of Nottingham, University Park, Nottingham NG7 2RD, UK.
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  • Hans V. Westerhoff,

    1. The Manchester Centre for Integrative Systems Biology, Manchester Interdisciplinary Biocentre, The University of Manchester, Manchester, UK
    2. Netherlands Institute for Systems Biology, VUA and UVA, Amsterdam, The Netherlands, EU
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  • Royston Goodacre,

    1. The Manchester Centre for Integrative Systems Biology, Manchester Interdisciplinary Biocentre, The University of Manchester, Manchester, UK
    2. The School of Chemistry, Manchester Interdisciplinary Biocentre, The University of Manchester, Manchester, UK
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  • Alan J. Dickson

    Corresponding author
    1. Faculty of Life Sciences, The University of Manchester, Michael Smith Building, Oxford Road, Manchester M13 9PT, UK; telephone: 0161 275 5101; fax: 0161 275 5082
    • Faculty of Life Sciences, The University of Manchester, Michael Smith Building, Oxford Road, Manchester M13 9PT, UK; telephone: 0161 275 5101; fax: 0161 275 5082.
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Abstract

Chinese hamster ovary (CHO) cells are the primary platform for commercial expression of recombinant therapeutic proteins. Obtaining maximum production from the expression platform requires optimal cell culture medium (and associated nutrient feeds). We have used metabolite profiling to define the balance of intracellular and extracellular metabolites during the production process of a CHO cell line expressing a recombinant IgG4 antibody. Using this metabolite profiling approach, it was possible to identify nutrient limitations, which acted as bottlenecks for antibody production, and subsequently develop a simple feeding regime to relieve these metabolic bottlenecks. This metabolite profiling-based strategy was used to design a targeted, low cost nutrient feed that increased cell biomass by 35% and doubled the antibody titer. This approach, with the potential for utilization in non-specialized laboratories, can be applied universally to the optimization of production of commercially important biopharmaceuticals. Biotechnol. Bioeng. 2011;108: 3025–3031. © 2011 Wiley Periodicals, Inc.

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