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IMMUNOBIOLOGY
From the Department of Research and Development,
Héma-Québec, Québec, Canada; and the Department of
Biochemistry and Microbiology, Laval University, Québec, Canada.
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 µg) 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. This article has been cited by other articles:
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| Copyright © 2002 by American Society of Hematology Online ISSN: 1528-0020 | |||||||||