title: Selection of a human anti-RhD monoclonal antibody for therapeutic use: impact of IgG glycosylation on activating and inhibitory Fc gamma R functions.
abstract: The substitution of plasmatic anti-RhD polyclonal antibodies by a monoclonal antibody (mAb) for preventing the hemolytic disease of the newborn (HDN) is an important issue due to supply and safety concerns. Since it has been suggested that FcgammaR are involved in the prevention of HDN, the in vitro functional properties of two anti-RhD mAbs differing through their glycosylation profiles were compared using FcgammaR-based assays to select a candidate mAb. T125(YB2/0), a low fucosylated antibody, bound strongly to both activating FcgammaRIII and inhibitory FcgammaRII, as opposed to its highly fucosylated counterpart. It also exerted a strong ADCC against RhD+ RBCs and a potent FcgammaRIIB-mediated inhibition of cytokine release. Moreover, an in vivo RhD+ red blood cells (RBCs) clearance assay showed that this antibody exhibits a RhD+ RBCs clearance as potent as polyclonal anti-RhD antibodies in NOD-SCID mice. Thus, T125(YB2/O) has been selected to be tested for the prevention of anti-RhD allo-immunization.
authors.affiliation: Unité INSERM 255, IFR58, Université René Descartes-Paris 5, Université Pierre et Marie Curie-Paris 6, Centre de Recherches Biomédicales des Cordeliers, Paris, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Sibéril
authors.forename: Christophe
authors.initials: C
authors.lastname: de Romeuf
authors.forename: Nicolas
authors.initials: N
authors.lastname: Bihoreau
authors.forename: Nadine
authors.initials: N
authors.lastname: Fernandez
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Meterreau
authors.forename: Annie
authors.initials: A
authors.lastname: Regenman
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Nony
authors.forename: Christine
authors.initials: C
authors.lastname: Gaucher
authors.forename: Arnaud
authors.initials: A
authors.lastname: Glacet
authors.forename: Sylvie
authors.initials: S
authors.lastname: Jorieux
authors.forename: Philippe
authors.initials: P
authors.lastname: Klein
authors.forename: Mark P
authors.initials: MP
authors.lastname: Hogarth
authors.forename: Wolf-Herman
authors.initials: WH
authors.lastname: Fridman
authors.forename: Dominique
authors.initials: D
authors.lastname: Bourel
authors.forename: Roland
authors.initials: R
authors.lastname: Béliard
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Teillaud
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D004912:Erythrocytes / Q000276:immunology; D006031:Glycosylation; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism*; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D051381:Rats; D017452:Receptors, IgG / Q000378:metabolism / Q000502:physiology*; D012204:Rh-Hr Blood-Group System / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; C499173:FCGR2B protein, human; C496124:FCGR3A protein, human; C485700:Fcgr3 protein, mouse; D007074:Immunoglobulin G; D017452:Receptors, IgG; D012204:Rh-Hr Blood-Group System; C026410:Rho(D) antigen