HUMAN RH-D MONOCLONAL-ANTIBODIES (BRAD-3 AND BRAD-5) CAUSE ACCELERATED CLEARANCE OF RH-D-BLOOD-CELLS AND SUPPRESSION OF RH-D IMMUNIZATION IN RH-D- VOLUNTEERS( RED)

The use of prophylactic anti-D to prevent Rh D immunization in Rh D- w omen and subsequent hemolytic disease in Rh D+ infants is widespread, but has led to shortages of the anti-D lg. With the aim of substitutin g monoclonal anti-D for Rh D prophylaxis, we have compared the abiliti es of monoclonal and polyclonal anti-D to clear ph D+ red blood cells (RBCs) infused into Rh D- male volunteers and to suppress Rh D immuniz ation. Two human monoclonal antibodies (MoAbs), BRAD-3 (lgG3) and BRAD -5 (IgG1), produced from stable Epstein-Barr virus-transformed B-lymph oblastoid cell lines, were selected because of their proven in vitro a ctivity in promoting RBC lysis in antibody-dependent cell-mediated cyt otoxicity assays. RBC clearance was assessed by intravenous injection of 3 mL of (51)chromium-labeled D+ RBCs into 27 volunteers 48 hours af ter intramuscular injection of monoclonal or polyclonal anti-D. Furthe r 3-mL injections of unlabeled D+ cells were administered at 6 and 9 m onths to induce immunization. Blood samples were taken throughout the 12-month period of study for the serologic detection of anti-D. The me an half-life (t(50%)) of RBCs in 7 recipients of 300 mu g BRAD-B (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 mu g BRAD-3 (mean t(50%) 12.7 hours) and in 1 individual administered 100 mu g BRAD-3 (t(50%) 41.0 hours). The rate of RBC clearance in both groups administered 300 mu g monoclonal anti-D correlated with the amount of antibody bound per cell, determi ned by flow cytometry. There was no evidence of primary immunization h aving 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 mon oclonal or polyclonal anti-D administered initially. Four of these res ponders were recipients of monoclonal anti-D (3 BRAD-3, 1 BRAD-5). One individual who received BRAD-5 produced accelerated clearance of Df R BCs at the third unprotected RBC challenge but did not seroconvert. Th is study shows that the human MoAbs BRAD-3 and BRAD-5 can prevent Rh D immunization, and indicates that they may be suitable replacements fo r the polyclonal anti-D presently used in prophylaxis of ph D hemolyti c disease of the newborn. This report is one of the first to show the therapeutic utility of blood group MoAbs. (C) 1995 by The American Soc iety of Hematology.