Trends in Glycosylation, Glycoanalysis and Glycoengineering of Therapeutic Antibodies and Fc-Fusion Proteins

Author(s): Alain Beck, Elsa Wagner-Rousset, Marie-Claire Bussat, Maryline Lokteff, Christine Klinguer-Hamour, Jean-François Haeuw, Liliane Goetsch, Thierry Wurch, Alain Van Dorsselaer, Nathalie Corvaia.

Journal Name:Current Pharmaceutical Biotechnology

Volume 9 , Issue 6 , 2008

Abstract:

Monoclonal antibodies (MAbs) are the fastest growing class of human pharmaceuticals. More than 20 MAbs have been approved and several hundreds are in clinical trials in various therapeutic indications including oncology, inflammatory diseases, organ transplantation, cardiology, viral infection, allergy, and tissue growth and repair. Most of the current therapeutic antibodies are humanized or human Immunoglobulins (IgGs) and are produced as recombinant glycoproteins in eukaryotic cells. Many alternative production systems and improved constructs are also being actively investigated. IgGs glycans represent only an average of around 3 % of the total mass of the molecule. Despite this low percentage, particular glycoforms are involved in essential immune effector functions. On the other hand, glycoforms that are not commonly biosynthesized in human may be allergenic, immunogenic and accelerate the plasmatic clearance of the linked antibody. These glyco-variants have to be identified, controlled and limited for therapeutic uses. Glycosylation depends on multiple factors like production system, selected clonal population, manufacturing process and may be genetically or chemically engineered. The present account reviews the glycosylation patterns observed for the current approved therapeutic antibodies produced in mammalian cell lines, details classical and state-of-the-art analytical methods used for the characterization of glycoforms and discusses the expected benefits of manipulating the carbohydrate components of antibodies by bio- or chemical engineering as well as the expected advantages of alternative biotechnological production systems developed for new generation of therapeutic antibodies and Fc-fusion proteins.

Keywords: Therapeutic antibody, Fc-fusion protein, mass spectrometry, capillary electrophoresis, glycoengineering, glycomics, glycoanalytics

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Article Details

VOLUME: 9
ISSUE: 6
Year: 2008
Page: [482 - 501]
Pages: 20
DOI: 10.2174/138920108786786411
Price: $58