title: Analysis of the control of the anti-gal immune response in a non-human primate by galactose alpha1-3 galactose trisaccharide-polyethylene glycol conjugate.
abstract: BACKGROUND
  The current limitation to the clinical application of xenotransplantation using pig organs is a rejection process that has been termed delayed xenograft rejection or acute vascular rejection. It is thought that acute vascular rejection may be mediated at least in part by both the continued synthesis, of preexisting, and the induction, posttransplantation, of antibodies against the carbohydrate moiety galalpha1-3gal that is present on glycoproteins and glycolipids of the pig endothelium. The synthesis of these antibodies has proven difficult to control with currently available immunosuppressive agents.
  
  
  METHODS
  We have synthesized galalpha1-3gal conjugated polyethylene glycol polymers that can bind to anti-galalpha1-3gal antibodies and tested their activity in non-human primates.
  
  
  RESULTS
  These conjugates when administered to non-human primates can substantially reduce the levels of preexisting and control the induction of anti-galalpha1-3gal antibodies. The level of circulating antibody-secreting cells that make anti-galalpha1-3gal antibodies is also reduced.
  
  
  CONCLUSIONS
  These alpha-gal polyethylene glycol conjugates may have the potential to control the anti-gal antibody response in a pig to primate organ transplant setting and may be a useful therapeutic agent in prolonging graft survival.
authors.affiliation: Nextran Inc., 303B College Road East, Princeton, NJ 08540, USA.
authors.forename: Lisa E
authors.initials: LE
authors.lastname: Diamond
authors.forename: Guerard W
authors.initials: GW
authors.lastname: Byrne
authors.forename: Alexander
authors.initials: A
authors.lastname: Schwarz
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Davis
authors.forename: David H
authors.initials: DH
authors.lastname: Adams
authors.forename: John S
authors.initials: JS
authors.lastname: Logan
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D000910:Antibodies, Heterophile / Q000097:blood* / Q000276:immunology; D001781:Blood Component Removal; D003326:Coronary Circulation; D004187:Disaccharides / Q000276:immunology* / Q000494:pharmacology; D006084:Graft Rejection / Q000276:immunology* / Q000517:prevention & control; D016027:Heart Transplantation / Q000276:immunology*; D008252:Macaca fascicularis; D010215:Papio; D011092:Polyethylene Glycols / Q000494:pharmacology; D013552:Swine; D014183:Transplantation, Heterologous / Q000276:immunology*
chemical_list: D000910:Antibodies, Heterophile; D004187:Disaccharides; C055075:galactosyl-(1-3)galactose; D011092:Polyethylene Glycols