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

• Published in: Blood 1995-09, Vol.86 (5), p.1701-1709
• Main Authors: KUMPEL, B. M, GOODRICK, M. J, PAMPHILON, D. H, FRASER, I. D, POOLE, G. D, MORSE, C, STANDEN, G. R, CHAPMAN, G. E, THOMAS, D. P, ANSTEE, D. J
• Format: Article
• Language: English
• Subjects: Adult; Antibodies - pharmacology; Antibodies, Monoclonal - biosynthesis; Antibodies, Monoclonal - isolation & purification; Antibodies, Monoclonal - pharmacology; B-Lymphocytes - immunology; Biological and medical sciences; Cell Line, Transformed; Erythrocytes - immunology; Erythrocytes - physiology; Hemolysis - immunology; Herpesvirus 4, Human; Humans; Immunization; Immunoglobulin G - biosynthesis; Immunoglobulin G - isolation & purification; Immunoglobulin G - pharmacology; Immunomodulators; Male; Medical sciences; Middle Aged; Pharmacology. Drug treatments; Rh-Hr Blood-Group System - immunology
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.v86.5.1701.bloodjournal8651701

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.