Abstract
Glycosylation is known to have an impact on pharmacokinetics and pharmacodynamics of therapeutic proteins. While the production of pharmaceutically desirable glycosylation forms of a therapeutic protein can in certain cases be influenced by the upstream process parameters, certain specialized glycan structures can only be produced in large quantities from cell lines that have been genetically engineered.
One particular case where a specialized glycostructure has a major impact on pharmacodynamic mode of action is the enhanced ADCC-effector function of afucosylated IgG1-type monoclonal antibodies. Here we describe the methodological details of a powerful yet simple glycoengineering approach targeted at the fucosylation machinery within eukaryotic cells. As an example we demonstrate the modification of the permanent avian cell line AGE1.CR.pIX which is characterized by a unique glycosylation machinery.
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Acknowledgments
The authors thank Dr. Veronique Blanchard, Dr. Markus Berger, and Dr. Matthias Kaup, Charite Berlin for very helpful discussions and support throughout the program. Parts of this work were supported by the Bundesministerium für Bildung und Forschung (InnoProfile 03IP511) and by the Sonnenfeld Foundation.
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Ogorek, C., Jordan, I., Sandig, V., von Horsten, H.H. (2012). Fucose-Targeted Glycoengineering of Pharmaceutical Cell Lines. In: Chames, P. (eds) Antibody Engineering. Methods in Molecular Biology, vol 907. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-61779-974-7_29
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DOI: https://doi.org/10.1007/978-1-61779-974-7_29
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