Functional in vivo characterization of human monoclonal anti-D in NOD-scid mice.
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.
Bazin
Renée
R
Department of Research and Development, Héma-Québec, Québec, Canada. rbazin@hema.quebec.qc.ca
Aubin
Eric
E
Boyer
Lucie
L
St-Amour
Isabelle
I
Roberge
Chantal
C
Lemieux
Réal
R
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
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