Improvement in human decay accelerating factor transgenic porcine kidney xenograft rejection with intravenous administration of gas914, a polymeric form of alphaGAL.
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.
Zhong
Robert
R
Department of Surgery, The University of Western Ontario, London, Ontario, Canada. zzhong@uwo.ca
Luo
Yigang
Y
Yang
Hongji
H
Garcia
Bertha
B
Ghanekar
Anand
A
Luke
Patrick
P
Chakrabarti
Subrata
S
Lajoie
Ginette
G
Phillips
M James
MJ
Katopodis
Andreas G
AG
Duthaler
Rudolf O
RO
Cattral
Mark
M
Wall
William
W
Jevnikar
Anthony
A
Bailey
Michele
M
Levy
Gary A
GA
Grant
David R
DR
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*
D000305:Adrenal Cortex Hormones; D018958:CD55 Antigens; D014312:Trisaccharides; C076569:alpha-galactosyl epitope; D003520:Cyclophosphamide