title: Trends in glycosylation, glycoanalysis and glycoengineering of therapeutic antibodies and Fc-fusion proteins.
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.
authors.affiliation: Centre d'Immunologie Pierre Fabre, 5 Avenue Napoléon III, F74160, Saint-Julien-en-Genevois, France. alain.beck@pierre-fabre.com
authors.forename: Alain
authors.initials: A
authors.lastname: Beck
authors.forename: Elsa
authors.initials: E
authors.lastname: Wagner-Rousset
authors.forename: Marie-Claire
authors.initials: MC
authors.lastname: Bussat
authors.forename: Maryline
authors.initials: M
authors.lastname: Lokteff
authors.forename: Christine
authors.initials: C
authors.lastname: Klinguer-Hamour
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Haeuw
authors.forename: Liliane
authors.initials: L
authors.lastname: Goetsch
authors.forename: Thierry
authors.initials: T
authors.lastname: Wurch
authors.forename: Alain
authors.initials: A
authors.lastname: Van Dorsselaer
authors.forename: Nathalie
authors.initials: N
authors.lastname: Corvaïa
mesh_terms: D000911:Antibodies, Monoclonal / Q000235:genetics / Q000276:immunology* / Q000627:therapeutic use*; D002241:Carbohydrates / Q000235:genetics / Q000276:immunology*; D015195:Drug Design; D004345:Drug Industry / Q000639:trends*; D006031:Glycosylation; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000235:genetics / Q000276:immunology*; D015202:Protein Engineering / Q000639:trends*
chemical_list: D000911:Antibodies, Monoclonal; D002241:Carbohydrates; D007141:Immunoglobulin Fc Fragments