ENZYMATIC REMODELING OF THE CARBOHYDRATE SURFACE OF A XENOGENIC CELL SUBSTANTIALLY REDUCES HUMAN-ANTIBODY BINDING AND COMPLEMENT-MEDIATED CYTOLYSIS

The major obstacle to successful discordant xenotransplantation is the phenomenon of hyperacute rejection (HAR). In the pig-to-primate disco rdant transplant setting, HAR results from the deposition of high-titr e anti-alpha-galactosyl antibodies and complement activation leading t o endothelial cell destruction and rapid graft failure. To overcome HA R, we developed an enzymatic carbohydrate remodelling strategy designe d to replace expression of the Gal alpha-1,3-Gal xenoepitope on the su rface of porcine cells with the nonantigenic universal donor human blo od group O antigen, the alpha-1,2-fucosyl lactosamine moiety (H-epitop e). Xenogenic cells expressing the human alpha-1,2-fucosyltransferase expressed high levels of the H-epitope and significantly reduced Gal a lpha-1,3-Gal expression. As a result, these cells were shown to be res istant to human natural antibody binding and complement-mediated cytol ysis.