Treatment with humanized monoclonal antibodies against CD80 and CD86 combined with sirolimus prolongs renal allograft survival in cynomolgus monkeys.
BACKGROUND
Co-stimulatory blockade has been shown to prolong allograft survival in different transplant models. We investigated the effect of combining humanized anti-CD80 and anti-CD86 monoclonal antibodies (mAb) with sirolimus in cynomolgus monkey renal transplant recipients.


METHODS
After renal transplantation, groups of four animals were treated daily with sirolimus, sirolimus and nine weekly doses of mAb, two weekly doses of mAb, or sirolimus and two weekly doses of mAb.


RESULTS
Survival was significantly better in monkeys treated with the combination of sirolimus and mAb when compared with treatment with either agent alone (P=0.0067 by log-rank analysis). When combined with sirolimus, nine weekly doses of mAb did not result in an additional survival benefit compared with only two mAb doses (P=0.74). None of the treatment regimens used in this study resulted in development of transplantation tolerance.


CONCLUSIONS
Sirolimus can be successfully combined with humanized mAb against CD80 and CD86. Induction with a short course of mAb is effective in prolonging allograft survival in combination with sirolimus.
Bîrsan
Tudor
T
Department of Cardiothoracic Surgery, Stanford University, Stanford, CA 94305-5407, USA.
Hausen
Bernard
B
Higgins
John P
JP
Hubble
Richard W
RW
Klupp
Jochen
J
Stalder
Mario
M
Celniker
Abbie
A
Friedrich
Stuart
S
O'Hara
Richard M
RM
Morris
Randall E
RE
D000818:Animals; D000911:Antibodies, Monoclonal / Q000097:blood / Q000627:therapeutic use*; D015703:Antigens, CD / Q000276:immunology*; D018122:B7-1 Antigen / Q000276:immunology*; D051940:B7-2 Antigen; D001706:Biopsy; D006085:Graft Survival / Q000187:drug effects / Q000276:immunology*; D006650:Histocompatibility Testing; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D016030:Kidney Transplantation / Q000276:immunology* / Q000473:pathology; D008252:Macaca fascicularis; D008562:Membrane Glycoproteins / Q000276:immunology*; D020123:Sirolimus / Q000494:pharmacology*; D013997:Time Factors; D014184:Transplantation, Homologous / Q000276:immunology
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497964:CD86 protein, human; D007166:Immunosuppressive Agents; D008562:Membrane Glycoproteins; D020123:Sirolimus