title: A human anti-D monoclonal antibody selected for enhanced FcgammaRIII engagement clears RhD+ autologous red cells in human volunteers as efficiently as polyclonal anti-D antibodies.
abstract: A human anti-RhD immunoglobulin G1 monoclonal antibody (mAb), R297, was tested in a phase I study to assess its ability to induce the clearance of antibody-coated autologous RhD+ red blood cells (RBCs) in healthy male volunteers. The clearance potency of R297 was compared with that of a marketed human polyclonal anti-D product (Rhophylac). This mAb has been selected for its ability to strongly engage Fc-gamma receptor IIIA and to mediate a potent antibody-dependent cell cytotoxicity (ADCC) against RhD+ RBCs. Autologous RhD+ RBCs were sensitized with either Rhophylac or R297 at three different coating percentages (25, 12.5 and 6.25%), before re-infusion. This phase I study showed that the human R297 mAb promoted rapid and complete clearance of RBCs, and showed activity that was at least as potent as the human polyclonal anti-D antibody preparation. Clearance of RBCs could still be observed when the percentage of R297 used to coat the RBCs was reduced to 6.25%. Finally, none of the adverse events was severe or considered to be related to R297. Thus, R297 is a promising candidate for the prevention of allo-immunization and represents a new generation of Fc-modified monoclonal antibodies with increased FcgammaRIII binding and increased ADCC.
authors.affiliation: Laboratoire Français du Fractionnement et des Biotechnologies, Les Ulis, Courtaboeuf Cedex, France. beliard@lfb.fr
authors.forename: Roland
authors.initials: R
authors.lastname: Beliard
authors.forename: Tony
authors.initials: T
authors.lastname: Waegemans
authors.forename: Dominique
authors.initials: D
authors.lastname: Notelet
authors.forename: Léna
authors.initials: L
authors.lastname: Massad
authors.forename: Frédéric
authors.initials: F
authors.lastname: Dhainaut
authors.forename: Christophe de
authors.initials: Cd
authors.lastname: Romeuf
authors.forename: Eric
authors.initials: E
authors.lastname: Guemas
authors.forename: Wouter
authors.initials: W
authors.lastname: Haazen
authors.forename: Dominique
authors.initials: D
authors.lastname: Bourel
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Teillaud
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Prost
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000276:immunology*; D000920:Antibody-Dependent Cell Cytotoxicity / Q000276:immunology; D004912:Erythrocytes / Q000276:immunology*; D006461:Hemolysis / Q000235:genetics / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D007518:Isoantibodies / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D017452:Receptors, IgG / Q000235:genetics / Q000276:immunology*; D018029:Rho(D) Immune Globulin / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; C445323:FCGR2A protein, human; C496124:FCGR3A protein, human; D007074:Immunoglobulin G; D007518:Isoantibodies; C061961:RHO(D) antibody; D017452:Receptors, IgG; D018029:Rho(D) Immune Globulin; D014409:Tumor Necrosis Factor-alpha