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Effect of Culture Conditions on IgM Antibody Structure, Pharmacokinetics and Activity

Bio/Technologyvolume 11pages387392 (1993) | Download Citation

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Abstract

Culture conditions affect the binding activity, charge heterogeneity, conformational stability, glycosylation, and pharmacokinetics of human monoclonal IgM HMAB-10058. The 10058 human/human/murine trioma was grown in serum-free airlift suspension culture, hollow fiber perfusion culture, or in nude mouse ascites. The ascites-produced antibody showed reduced conformational stability, greater charge and glycoform heterogeneity, and a lower average degree of sialylation than the in vitro culture-produced material. Mean residence time after IV injection in rats was approximately 80-fold greater for the ascites culture-produced material, but specific binding activity was less than 5% of that for the airlift-produced material. In vitro culture in serum-supplemented media (in a hollow fiber perfusion reactor or in shake-flasks) resulted in antibody with pharmacokinetics intermediate between the serum-free airlift and ascites-produced materials. Incubation of airlift-produced antibody in ascites fluid also resulted in material with intermediate pharmacokinetics. Conclusions regarding the effect of culture conditions on antibody product cannot be generalized, as in vitro-produced antibody derived from two related cell lines (HMAB-10233 and HMAB-10390) had long mean residence times similar to that of ascites-produced HMAB-10058.

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Author information

Author notes

    • J. Winkelhake

    Present address: Cytel, San Diego, CA

    • J. Young

    Present address: Amgen, Thousand Oaks, CA

    • B. Moyer

    Present address: Diatech, Londonderry, NH

    • R. Bauer

    Present address: Xoma, Berkeley, CA

    • J. Andya

    Present address: Genentech, S. San Francisco, CA

    • J. Thomson

    Present address: Synergen, Boulder, CO

  1. T. Patel and R. Parekh: Oxford GlycoSystems, Ltd., Hitching Court, Abingdon, Oxford OX14 1RG, U.K.

  2. B. L. Maiorella: Corresponding author.

Affiliations

  1. Chiron Corp., 4560 Horton Street, Emeryville, CA, 94608

    • B. L. Maiorella
    •  & M. Hora

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DOI

https://doi.org/10.1038/nbt0393-387

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