A human anti‐D monoclonal antibody selected for enhanced FcγRIII engagement clears RhD+ autologous red cells in human volunteers as efficiently as polyclonal anti‐D antibodies

Summary 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 FcγRIII binding and increased ADCC.