title: Improvement in human decay accelerating factor transgenic porcine kidney xenograft rejection with intravenous administration of gas914, a polymeric form of alphaGAL.
abstract: BACKGROUND
  The present study was undertaken to determine whether intravenous administration of GAS914, a polymeric form of alphaGal, would minimize porcine kidney xenograft rejection in baboons. Human decay accelerating factor renal xenografts were transplanted into 16 baboon recipients.
  
  
  METHODS
  Baseline immunosuppression for all groups included cyclosporine A, cyclophosphamide, SDZ-RAD, and methylprednisolone. Group 1 received only baseline immunosuppression; group 2 animals received low-dose GAS914 with baseline immunosuppression; group 3 animals received high dose GAS914 with high-dose baseline immunosuppression; and animals from group 4 received high-dose GAS914 and low-dose baseline immunosuppression.
  
  
  RESULTS
  None of the animals in this study developed hyperacute rejection. Intravenous administration of GAS914 significantly reduced xenoreactive antibodies as measured by antiporcine hemolytic assays and anti-Gal (immunoglobulin [Ig] G and IgM) antibody assays. Rejection was less severe in the GAS914-treated group. Only 25% (3 of 12) of GAS914-treated animals were killed as a result of rejection, whereas 75% (three of four) of non-GAS914-treated animals were killed because of terminal rejection (P<0.01). Protocol biopsies demonstrated that the degree of acute humoral xenograft rejection (AHXR) was reduced in the GAS914-treated animals compared with non-GAS914-treated animals.
  
  
  CONCLUSIONS
  The intravenous administration of GAS914 reduces xenoreactive antibody levels and reduces the degree of porcine kidney xenograft rejection, but does not improve survival. AHXR and drug toxicity remain major barriers to the long-term success of xenotransplantation.
authors.affiliation: Department of Surgery, The University of Western Ontario, London, Ontario, Canada. zzhong@uwo.ca
authors.forename: Robert
authors.initials: R
authors.lastname: Zhong
authors.forename: Yigang
authors.initials: Y
authors.lastname: Luo
authors.forename: Hongji
authors.initials: H
authors.lastname: Yang
authors.forename: Bertha
authors.initials: B
authors.lastname: Garcia
authors.forename: Anand
authors.initials: A
authors.lastname: Ghanekar
authors.forename: Patrick
authors.initials: P
authors.lastname: Luke
authors.forename: Subrata
authors.initials: S
authors.lastname: Chakrabarti
authors.forename: Ginette
authors.initials: G
authors.lastname: Lajoie
authors.forename: M James
authors.initials: MJ
authors.lastname: Phillips
authors.forename: Andreas G
authors.initials: AG
authors.lastname: Katopodis
authors.forename: Rudolf O
authors.initials: RO
authors.lastname: Duthaler
authors.forename: Mark
authors.initials: M
authors.lastname: Cattral
authors.forename: William
authors.initials: W
authors.lastname: Wall
authors.forename: Anthony
authors.initials: A
authors.lastname: Jevnikar
authors.forename: Michele
authors.initials: M
authors.lastname: Bailey
authors.forename: Gary A
authors.initials: GA
authors.lastname: Levy
authors.forename: David R
authors.initials: DR
authors.lastname: Grant
mesh_terms: D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000818:Animals; D030801:Animals, Genetically Modified; D018958:CD55 Antigens / Q000502:physiology*; D003520:Cyclophosphamide / Q000627:therapeutic use; D006084:Graft Rejection / Q000517:prevention & control*; D006801:Humans; D007668:Kidney / Q000473:pathology; D016030:Kidney Transplantation / Q000276:immunology* / Q000401:mortality; D010215:Papio; D013552:Swine; D014183:Transplantation, Heterologous / Q000276:immunology*; D014312:Trisaccharides / Q000008:administration & dosage*
chemical_list: D000305:Adrenal Cortex Hormones; D018958:CD55 Antigens; D014312:Trisaccharides; C076569:alpha-galactosyl epitope; D003520:Cyclophosphamide