Selection of a human anti-RhD monoclonal antibody for therapeutic use:: Impact of IgG glycosylation on activating and inhibitory FcγR 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 Fc gamma R 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 Fc gamma R-based assays to select a candidate mAb. T125(YB2/0), a low fucosylated antibody, bound strongly to both activating Fc yRIII and inhibitory Fc gamma RII, as opposed to its highly fucosylated counterpart. It also exerted a strong ADCC against RhD+ RBCs and a potent Fc gamma RIIB-mediated inhibition of cytokine release. Moreover, an in vivo RhD+ red blood cells (PBCs) 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. (c) 2005 Elsevier Inc. All rights reserved.