title: Functional in vivo characterization of human monoclonal anti-D in NOD-scid mice.
abstract: The prophylaxis of the hemolytic disease of the newborn requires significant amounts of plasma-derived polyclonal human anti-D. Because of procurement problems, there is a growing interest in replacing plasma-derived anti-D by in vitro-produced human monoclonal anti-D. Hundreds of monoclonal anti-D have been prepared, but the selection of the most potent for in vivo use is difficult because it cannot be predicted by in vitro characterization. This study evaluated the possibility of using nonobese diabetic/severe combined immunodeficient (NOD-scid) mice for the in vivo evaluation of human monoclonal anti-D. Human red blood cells (RBCs) were found to circulate normally in the blood of NOD-scid mice previously injected with a physiologic amount of human immunoglobulin G (10 mg). The addition of a small amount of anti-D (1 to 5 microg) resulted in the clearance of Rh D(+) RBCs within 4 hours. The comparative testing of 8 monoclonal anti-Ds showed a wide range of potency (15% to 87%) relative to plasma-derived polyclonal anti-D. There was no strong correlation between the in vivo potency index and the immunoglobulin G isotype, affinity, or fine specificity of the antibodies. These results show the usefulness of NOD-scid mice for the initial in vivo screening of human monoclonal anti-D before testing the most active antibodies in clinical trials done in human volunteers.
authors.affiliation: Department of Research and Development, Héma-Québec, Québec, Canada. rbazin@hema.quebec.qc.ca
authors.forename: Renée
authors.initials: R
authors.lastname: Bazin
authors.forename: Eric
authors.initials: E
authors.lastname: Aubin
authors.forename: Lucie
authors.initials: L
authors.lastname: Boyer
authors.forename: Isabelle
authors.initials: I
authors.lastname: St-Amour
authors.forename: Chantal
authors.initials: C
authors.lastname: Roberge
authors.forename: Réal
authors.initials: R
authors.lastname: Lemieux
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000494:pharmacology; D000915:Antibody Affinity; D000918:Antibody Specificity; D002470:Cell Survival / Q000276:immunology; D004353:Drug Evaluation, Preclinical / Q000379:methods; D017707:Erythrocyte Transfusion; D004912:Erythrocytes / Q000276:immunology; D006461:Hemolysis / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000008:administration & dosage / Q000494:pharmacology; D007132:Immunoglobulin Isotypes / Q000008:administration & dosage / Q000494:pharmacology; D007518:Isoantibodies / Q000008:administration & dosage / Q000494:pharmacology*; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D012204:Rh-Hr Blood-Group System / Q000276:immunology*; D018029:Rho(D) Immune Globulin
chemical_list: D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D007132:Immunoglobulin Isotypes; D007518:Isoantibodies; C061961:RHO(D) antibody; D012204:Rh-Hr Blood-Group System; D018029:Rho(D) Immune Globulin; C026410:Rho(D) antigen