Selection of a human anti-RhD monoclonal antibody for therapeutic use: impact of IgG glycosylation on activating and inhibitory Fc gamma R functions.
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.
Sibéril
Sophie
S
Unité INSERM 255, IFR58, Université René Descartes-Paris 5, Université Pierre et Marie Curie-Paris 6, Centre de Recherches Biomédicales des Cordeliers, Paris, France.
de Romeuf
Christophe
C
Bihoreau
Nicolas
N
Fernandez
Nadine
N
Meterreau
Jean-Luc
JL
Regenman
Annie
A
Nony
Emmanuel
E
Gaucher
Christine
C
Glacet
Arnaud
A
Jorieux
Sylvie
S
Klein
Philippe
P
Hogarth
Mark P
MP
Fridman
Wolf-Herman
WH
Bourel
Dominique
D
Béliard
Roland
R
Teillaud
Jean-Luc
JL
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*
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