Monoclonal anti-D for prophylaxis of RhD haemolytic disease of the newborn

Abstract

The incidence of Rh D haemolytic disease of the fetus and newborn has been dramatically reduced by the prophylactic administration of anti-D immunoglobulin to Rh D-negative women. This preventive treatment depends on adequate supplies of anti-D derived from plasma of immunised donors, and replacement with monoclonal anti-D would be advantageous. Two monoclonal antibodies, BRAD-3 (IgG3) and BRAD-5 (IgG1) have been produced from EBV-transformed B-lymphoblastoid cell lines in Bristol and extensively characterised. Both have shown good (but differing) functional activities, determined by study of interactions of anti-D coated red cells with effector cells bearing IgG Fc receptors. Phase I clinical trials using Rh D negative male volunteers were undertaken in Bristol. The plasma half lives of BRAD-3 and BRAD-5 were characteristic for their IgG subclass, and both anti-D mediated accelerated circulatory clearance of D-positive red cells infused two days after i.m. injection of the antibodies. BRAD-3 and BRAD-5 were then shown to protect the volunteers from mounting a primary anti-D response to these D-positive red cells, and thus they may be suitable for Rh D prophylaxis of Rh D-negative women.