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Monoclonal Antibody Glycoengineering for Biopharmaceutical Quality Assurance

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Cell Culture Engineering and Technology

Part of the book series: Cell Engineering ((CEEN,volume 10))

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Abstract

Therapeutic monoclonal antibodies (mAbs) are glycoproteins that contain a pair of N-glycosylation sites on their constant fragment and are widely prescribed for the treatment of several types of cancer and autoimmune disorders. Glycosylation is considered a critical quality attribute of mAbs because it is essential to the safety, pharmacokinetics, and pharmacodynamics of these life-saving biopharmaceuticals. High degrees of glycosylation variability have been observed across different production campaigns of the same mAb product and arise from the numerous biological reactions involved in the glycosylation process, their sensitivity to cell culture conditions, and the genetic background of the production host. Due to its influence in defining the quality of mAb products, substantial effort has been made to develop strategies that minimise mAb glycosylation heterogeneity. This chapter recapitulates the progress made towards controlling mAb glycosylation within the context of biopharmaceutical quality assurance. The chapter presents a critical review of the vast number of (i) cellular, (ii) metabolic, and (iii) in vitro glycoengineering strategies that have been developed to enhance the quality of therapeutic mAbs. We conclude by outlining how these strategies can be combined to achieve the complex task of manufacturing homogenous mAb glycoforms that elicit optimal therapeutic outcomes in the clinic.

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The authors gratefully acknowledge funding by the Mexican Council for Science and Technology (CONACyT) (grant number 438330), The Irish Research Council (grant number GOIPG/2017/1049) and Science Foundation Ireland (SFI), via the SSPC Research Centre for Pharmaceuticals (grant number 12/RC/2275_P2).

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    Itzcóatl Gómez Aquino & Ioscani Jiménez del Val

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    Ralf Pörtner

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Aquino, I.G., del Val, I.J. (2021). Monoclonal Antibody Glycoengineering for Biopharmaceutical Quality Assurance. In: Pörtner, R. (eds) Cell Culture Engineering and Technology. Cell Engineering, vol 10. Springer, Cham. https://doi.org/10.1007/978-3-030-79871-0_6

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