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Enzymatic remodelling of the carbohydrate surface of a xenogenic cell substantially reduces human antibody binding and complement-mediated cytolysis

Nature Medicine volume 1, pages 1261–1267 (1995)Cite this article

Abstract

The major obstacle to successful discordant xenotransplantation is the phenomenon of hyperacute rejection (HAR). In the pig-to-primate discordant transplant setting, HAR results from the deposition of high-titre anti-α-galactosyl antibodies and complement activation leading to endothelial cell destruction and rapid graft failure. To overcome HAR, we developed an enzymatic carbohydrate remodelling strategy designed to replace expression of the Galα-1,3-Gal xenoepitope on the surface of porcine cells with the non-antigenic universal donor human blood group O antigen, the α-1,2-fucosyl lactosamine moiety (H-epitope). Xenogenic cells expressing the human α-1,2-fucosyltransferase expressed high levels of the H-epitope and significantly reduced Galα-1,3-Cal expression. As a result, these cells were shown to be resistant to human natural antibody binding and complement-mediated cytolysis.

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Author information

Authors and Affiliations

  1. Molecular Immunogenetics Laboratory, Austin Research Institute, Heidelberg, Vic., 3084, Australia

    Mauro S. Sandrin, Effie Mouthtouris, Narin Osman, Shlomo Cohney & Ian F.C. Mckenzie

  2. Alexion Pharmaceuticals Inc., 25 Science Park, New Haven, Connecticut, 06511, USA

    William L. Fodor, Scott A. Rollins, Edward R. Guilmette, Eva Setter & Stephen P. Squinto

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  1. Mauro S. Sandrin
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Sandrin, M., Fodor, W., Mouthtouris, E. et al. Enzymatic remodelling of the carbohydrate surface of a xenogenic cell substantially reduces human antibody binding and complement-mediated cytolysis. Nat Med 1, 1261–1267 (1995). https://doi.org/10.1038/nm1295-1261

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