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Human Rh D monoclonal antibodies (BRAD-3 and BRAD-5) cause accelerated
clearance of Rh D+ red blood cells and suppression of Rh D immunization in
Rh D- volunteers
BM Kumpel, MJ Goodrick, DH Pamphilon, ID Fraser, GD Poole, C Morse, GR Standen, GE Chapman, DP Thomas and DJ Anstee
International Blood Group Reference Laboratory, Bristol, UK.
The use of prophylactic anti-D to prevent Rh D immunization in Rh D- women
and subsequent hemolytic disease in Rh D+ infants is widespread, but has
led to shortages of the anti-D Ig. With the aim of substituting monoclonal
anti-D for Rh D prophylaxis, we have compared the abilities of monoclonal
and polyclonal anti-D to clear Rh D+ red blood cells (RBCs) infused into Rh
D- male volunteers and to suppress Rh D immunization. Two human monoclonal
antibodies (MoAbs), BRAD-3 (IgG3) and BRAD-5 (IgG1), produced from stable
Epstein-Barr virus-transformed B-lymphoblastoid cell lines, were selected
because of their proven in vitro activity in promoting RBC lysis in
antibody-dependent cell- mediated cytotoxicity assays. RBC clearance was
assessed by intravenous injection of 3 mL of 51chromium-labeled D+ RBCs
into 27 volunteers 48 hours after intramuscular injection of monoclonal or
polyclonal anti-D. Further 3-mL injections of unlabeled D+ cells were
administered at 6 and 9 months to induce immunization. Blood samples were
taken throughout the 12-month period of study for the serologic detection
of anti-D. The mean half-life (t50%) of RBCs in 7 recipients of 300
micrograms BRAD-5 (5.9 hours) was similar to that in 8 recipients of 500 IU
polyclonal anti-D (5.0 hours), whereas D+ cells were cleared more slowly in
some of the 8 subjects injected with 300 micrograms BRAD- 3 (mean t50% 12.7
hours) and in 1 individual administered 100 micrograms BRAD-3 (t50% 41.0
hours). The rate of RBC clearance in both groups administered 300
micrograms monoclonal anti-D correlated with the amount of antibody bound
per cell, determined by flow cytometry. There was no evidence of primary
immunization having occurred in any subject after 6 months of follow-up.
Five of 24 subjects produced anti- D after one or two further injections of
RBCs, confirming that they were responders who had been protected by the
monoclonal or polyclonal anti-D administered initially. Four of these
responders were recipients of monoclonal anti-D (3 BRAD-3, 1 BRAD-5). One
individual who received BRAD-5 produced accelerated clearance of D+ RBCs at
the third unprotected RBC challenge but did not seroconvert. This study
shows that the human MoAbs BRAD-3 and BRAD-5 can prevent Rh D immunization,
and indicates that they may be suitable replacements for the polyclonal
anti-D presently used in prophylaxis of Rh D hemolytic disease of the
newborn.(ABSTRACT TRUNCATED AT 400 WORDS)
Volume 86,
Issue 5,
pp. 1701-1709,
09/01/1995
Copyright © 1995 by The American Society of Hematology
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