Xenogeneic organ transplantation

Current Opinion in Biotechnology

Volumn 7, Issue 6, 1996, Pages 641-645

  Squinto, Stephen P ^a  

^a ALEXION PHARMACEUTICALS   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

COMPLEMENT INHIBITOR;

COMPLEMENT ACTIVATION; COST BENEFIT ANALYSIS; GRAFT REJECTION; HEALTH CARE COST; HISTOINCOMPATIBILITY; IMMUNOMODULATION; NONHUMAN; ORGAN TRANSPLANTATION; PRIMATE; PRIORITY JOURNAL; SHORT SURVEY; SWINE; VASCULAR ENDOTHELIUM; XENOTRANSPLANTATION;

ANIMALIA; PRIMATES; SUS SCROFA;

EID: 0030560648     PISSN: 09581669     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0958-1669(96)80076-0     Document Type: Article

References (26)

1. Cozzi E, White DJG. The generation of transgenic pigs as potential organ donors for humans. of special interest Nat Med. 1:1995;964-966 Cozzi and White describe a rather significant effort to generate transgenic pigs that express sufficiently high levels of the human complement inhibitor, CD55 or DAF. Detailed analysis of the transgenic effort to screen large numbers of founder animals from which a herd is derived is described. This is the first report demonstrating the efficiency with which transgenic pigs expressing high levels of DAF can be achieved.
2. Animal-to-human transplants: the ethics of xenotransplantation. 1996;Nuffield Council on Bioethics, London.
3. Xenotransplantation; Science, Ethics, and Public Policy. 1996;Institute of Medicine, National Academy Press, Washington DC.
4. Scientific Research Report. 1995;United Network for Organ Sharing, Richmond, VA.
5. Woods JL. Health Services Research. 1992;219-238 United States Public Health Service, Washington, DC.
6. Platt JL, Lindman BJ, Chen H, Spitalnik S, Bach F. Endothelial antigens recognized by xenoreactive antibodies. Transplantation. 50:1990;817-822.
7. Sommerville CA, D'Apice AJF. Future directions in transplantation: xenotransplantation. Kidney Int. 44:1993;112-121. (suppl 42).
8. Oriol R, Ye Y, Koren E, Cooper DKC. Carbohydrate antigens of pig tissues reacting with human natural antibodies as potential targets for hyperacute rejection in pig-to-man xenotransplantation. Transplantation. 56:1993;1433-1442.
9. Galili U, Clark MR, Shohet SB, Buehler J, Macher BA. Evolutionary relationship between the natural anti-Gal antibody and the Galα1→3Gal epitope in primates. Proc Natl Acad Sci USA. 84:1987;1369-1373.
10. Sandrin MS, Vaughan HA, Dabkoski PL, McKenzie IFC. Anti-pig IgM antibodies in human serum reacts predominately with the Gal(α1,3)Gal epitopes. Proc Natl Acad Sci USA. 90:1993;11391-11395.
11. Larsen RD, Riverra-Marrero CA, Ernst LK, Cummings RD, Lowe JB. Frameshift and non-sense mutations in a human genomic sequence homologous to a murine UDP - Gal:B-Gal1,4-D-GlcNAcα1,3-galactosyl-transferase cDNA. J Biol Chem. 265:1990;7055-7061.
12. Sandrin MS, Vaughan HA, McKenzie IFC. Identification of Galα(1→3)Gal as the major epitope for pig-to-human vascularized xenografts. Transplant Rev. 8:1994;134-149.
13. Leventhal JR, Dalmasso AP, Cromwell JW, Platt JL, Manivel CJ, Bolman RM III, Matas AJ. Prolongation of cardiac xenograft survival by depletion of complement. Transplantation. 55:1993;857-866.
14. Pruitt SK, Kirk AD, Bollinger RR, Marsh HC Jr, Collins BH, Levin JL, Mault JR, Heinle JS, Ibrahim S, Rudolph AR, et al. The effect of soluble complement receptor type 1 on hyperacute rejection of porcine xenografts. Transplantation. 57:1994;363-370.
15. Cooper DKC, Koren E, Oriol R. Oligosaccharides and discordant xenotransplantation. Immunol Rev. 141:1994;31-58.
16. Fodor WL, Williams BL, Matis LA, Madri JA, Rollins SA, Knight JW, Velander W, Squinto SP. Expression of a functional human complement inhibitor in a transgenic pig as a model for the prevention of xenogeneic hyperacute organ rejection. Proc Natl Acad Sci USA. 91:1994;11153-11157.
17. McCurry KR, Kooyman DL, Alvarado CG, Cotterell AH, Martin MJ, Logan JS, Platt JL. Human complement regulatory proteins protect swine-to-primate cardiac xenografts from humoral injury. of special interest Nat Med. 1:1995;423-427 These authors describe a 'painting' technology used to generate transgenic pigs expressing human complement inhibitors. The globin promoter is used to drive expression of GPI-anchored human complement inhibitor proteins in the ethryocytes of the transgenic pigs. The GPI-containing proteins can 'jump' to the endothelial cells of the pig organs and provide transient protection against human complement. This is the first evidence that human complement inhibitors can provide transient protection from human complement following pig-to-primate organ transplantation.
18. Fodor WL, Squinto SP. Engineering of transgenic pigs for xenogeneic organ transplantation. of special interest Xenobiotica. 3:1995;23-25 Fodor and I summarize our efforts to engineer transgenic pigs to express the human complement inhibitor CD59. Also described is the rather ubiquitious expression of CD59 in tissues and organs of F1 generation transgenic pigs using a class I minigene to drive expression.
19. Rollins SA, Zhao J, Ninomiya H, Sims PJ. Inhibition of homologous complement by CD59 is mediated by a species-selective recognition conferred through binding of C8 within C5b-8 or C9 within C5b-9. J Biol Chem. 146:1991;2345-2352.
20. Hamilton KK, Hattori R, Esmon CT, Sims PJ. Complement proteins C5b-9 induce vesiculation of the endothelial plasma membrane and expose catalytic surface for assembly of the prothrombinase enzyme complex. J Biol Chem. 265:1990;3809-3813.
21. Hattori R, Hamilton KK, McEver RP, Sims PJ. Complement proteins C5b-9 induce secretion of high molecular weight multimers of von Willebrand factor and translocation of granule membrane protein GMP-140 to the cell surface. J Biol Chem. 264:1989;9053-9060.
22. Zhao J, Rollins SA, Maher SE, Bothwell ALM, Sims PJ. Amplified gene expression in CD59-transfected Chinese hamster ovary cells confers protection against the membrane attack complex of human complement. J Biol Chem. 266:1991;13418-13422.
23. Kennedy SP, Rollins SA, Burton WV, Sims PJ, Bothwell ALM, Squinto SP, Zavoico GG. Protection of porcine aortic endothelial cells from complement-mediated cell lysis and activation by recombinant human CD59. Transplantation. 57:1994;1494-1501.
24. Kroshus TJ, Bolman RM III, Dalmasso AP, Rollins SA, Williams Squinto SP, Fodor WL. Expression of human CD59 in transgenic pig organs enhances survival in an ex vivo xenogeneic perfusion model. Transplantation. 61:1996;1513-1521.
25. Sandrin MS, Fodor WL, Mouhtouris E, Osman N, Cohney S, Rollins SA, Guilmette ER, Setter E, Squinto SP, McKenzie IFC. Enzymatic remodelling of the carbohydrate surface of a xenogeneic cell substantially reduces human antibody binding and complement-mediated cytolysis. of outstanding interest Nat Med. 1:1995;1261-1267 These authors describe a novel gene engineering approach that results in an enzymatic remodeling of the carbohydrate composition of xenografts and xenogeneic cells. This approach utilizes intracellular enzyme competition to replace the highly antigenic α1,3-galactosyl-terminal carbohydrate with a human carbohydrate structure that is inert with regard to the human immune system. The authors demonstrate that the H-transferase enzyme can effectively outcompete the gal-transferase enzyme and replace the α-Gal carbohydrate epitope with a nonimmunogenic α1,2-fucosyl residue. As a consequence of this engineering strategy, both in vitro with xenogeneic cells and in vivo in transgenic mice, xenografts are not recognized by human antibodies and survive when challenged with human serum.
26. Fodor WL, Rollins SA, Guilmette ER, Setter E, Squinto SP. A novel bifunctional chimeric complement inhibitor that regulates C3 convertase and formation of the membrane attack complex. J Immunol. 155:1995;4135-4138.