Efficacy of RhD monoclonal antibodies in clinical trials as replacement therapy for prophylactic anti-D immunoglobulin: more questions than answers

Vox Sang. 2007 Aug;93(2):99-111. doi: 10.1111/j.1423-0410.2007.00945.x.

Abstract

Prophylactic anti-D is a very safe and effective therapy for the suppression of D-immunization and prevention of haemolytic disease of the foetus and newborn. The primary mode of action of anti-D is rapid clearance of fetal D-positive red cells from the maternal circulation, mediated by interactions with immunoglobulin G Fc receptors on macrophages in the spleen. Many anti-D monoclonal antibodies (mAb) have been produced by a variety of methods. Twelve anti-D mAbs were tested in eight studies for their ability to mediate clearance of autologous red cells, and 13 antibodies studied in seven trials of the clearance of D-positive red cells injected into D-negative subjects. Antibodies produced by human B-cell lines, mouse-human heterohybridomas and Chinese hamster ovary cells varied in their activity with none being quite as effective as polyclonal anti-D. However, clearance mediated by recombinant anti-D produced by rat YB2/0 cells was extremely rapid, faster than polyclonal anti-D, but with haemolysis and some hepatic accumulation of red cells observed in one study. Two human anti-D mAbs prevented D-immunization. In contrast, anti-D mAbs from heterohybridomas increased the incidence and rapidity of anti-D responses. It is hypothesised that unnatural glycosylation of monoclonal anti-D produced by some cell lines may have caused these unexpected results. In some antibodies, unusual oligosaccharides on anti-D may have affected binding to Fc receptors resulting in reduced red cell clearance. For others, non-human glycoforms of anti-D might have bound to innate immune recognition molecules promoting pro-inflammatory reactions. These extensive data on the clinical activity of monoclonal anti-D produced by cell lines derived from four species will inform the future development of monoclonal anti-D for RhD prophylaxis.

Publication types

  • Review

MeSH terms

  • Antibodies, Monoclonal / pharmacokinetics
  • Antibodies, Monoclonal / therapeutic use*
  • Clinical Trials as Topic / methods
  • Humans
  • Immunoglobulins, Intravenous / therapeutic use
  • Isoantibodies / therapeutic use
  • Premedication
  • Receptors, Fc / metabolism
  • Recombinant Proteins / pharmacokinetics
  • Recombinant Proteins / therapeutic use
  • Rh-Hr Blood-Group System / immunology*
  • Rho(D) Immune Globulin

Substances

  • Antibodies, Monoclonal
  • Immunoglobulins, Intravenous
  • Isoantibodies
  • RHO(D) antibody
  • Receptors, Fc
  • Recombinant Proteins
  • Rh-Hr Blood-Group System
  • Rho(D) Immune Globulin
  • Rho(D) antigen