title: Impact of Glycosylation on Effector Functions of Therapeutic IgG.
abstract: Human IgG has only one conserved glycosylation site located in the Cγ2 domain of the Fc region that accounts for the presence of two sugar moieties per IgG. These IgG sugar cores play a critical role in a number of IgG effector functions. In the present review, we describe the main characteristics of IgG Fc glycosylation and some abnormalities of serum IgG glycosylation. We also discuss how glycosylation impacts on monoclonal antibodies (mAbs) and IVIg effector functions and how these molecules can be engineered. Several therapeutic antibodies have now been engineered to be no- or low-fucose antibodies and are currently tested in clinical trials. They exhibit an increased binding to activating FcγRIIIA and trigger a strong antibody-dependent cell cytotoxicity (ADCC) as compared to their highly-fucosylated counterparts. They represent a new generation of therapeutic antibodies that are likely to show a better clinical efficacy in patients, notably in cancer patients where cytotoxic antibodies are needed.
authors.affiliation: INSERM UMRS 872, Paris, F-75006 France. riad.abes@crc.jussieu.com.|Cordeliers Research Center, Université Pierre & Marie Curie, UMRS 872, Paris, F-75006, France. riad.abes@crc.jussieu.com.|Université Paris-Descartes, UMRS 872, Paris, F-75006 France. riad.abes@crc.jussieu.com.|Laboratoire français du Fractionnement et des Biotechnologies (LFB), Les Ulis, France. riad.abes@crc.jussieu.com.
authors.forename: Riad
authors.initials: R
authors.lastname: Abès
authors.affiliation: INSERM UMRS 872, Paris, F-75006 France. jean-luc.teillaud@crc.jussieu.fr.|Cordeliers Research Center, Université Pierre & Marie Curie, UMRS 872, Paris, F-75006, France. jean-luc.teillaud@crc.jussieu.fr.|Université Paris-Descartes, UMRS 872, Paris, F-75006 France. jean-luc.teillaud@crc.jussieu.fr.
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Teillaud
keywords: Fc receptor; IgG; antibody; glycosylation