Treatment with humanized monoclonal antibodies against CD80 and CD86 combined with sirolimus prolongs renal allograft survival in cynomolgus monkeys.

Abstract:

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.

journal_name

Transplantation

journal_title

Transplantation

authors

Bîrsan T,Hausen B,Higgins JP,Hubble RW,Klupp J,Stalder M,Celniker A,Friedrich S,O'Hara RM,Morris RE

doi

10.1097/01.TP.0000066806.10029.7A

subject

Has Abstract

pub_date

2003-06-27 00:00:00

pages

2106-13

issue

12

eissn

0041-1337

issn

1534-6080

journal_volume

75

pub_type

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