Analysis of the control of the anti-gal immune response in a non-human primate by galactose alpha1-3 galactose trisaccharide-polyethylene glycol conjugate.
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.
Diamond
Lisa E
LE
Nextran Inc., 303B College Road East, Princeton, NJ 08540, USA.
Byrne
Guerard W
GW
Schwarz
Alexander
A
Davis
Thomas A
TA
Adams
David H
DH
Logan
John S
JS
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*
D000910:Antibodies, Heterophile; D004187:Disaccharides; C055075:galactosyl-(1-3)galactose; D011092:Polyethylene Glycols