Bîrsan Tudor, Hausen Bernard, Higgins John P, Hubble Richard W, Klupp Jochen, Stalder Mario, Celniker Abbie, Friedrich Stuart, O'Hara Richard M, Morris Randall E
Department of Cardiothoracic Surgery, Stanford University, Stanford, CA 94305-5407, USA.
Transplantation. 2003 Jun 27;75(12):2106-13. doi: 10.1097/01.TP.0000066806.10029.7A.
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.
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.
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.
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.
共刺激阻断已被证明可延长不同移植模型中的同种异体移植物存活时间。我们研究了将人源化抗CD80和抗CD86单克隆抗体（mAb）与西罗莫司联合应用于食蟹猴肾移植受者的效果。
肾移植后，将四组动物每日分别用西罗莫司、西罗莫司和九周剂量的mAb、两周剂量的mAb或西罗莫司和两周剂量的mAb进行治疗。
与单独使用任何一种药物治疗相比，联合使用西罗莫司和mAb治疗的猴子存活情况明显更好（对数秩分析P = 0.0067）。与仅使用两剂mAb相比，九周剂量的mAb与西罗莫司联合使用时并未带来额外的存活益处（P = 0.74）。本研究中使用的任何治疗方案均未导致移植耐受的发生。
西罗莫司可成功与人源化抗CD80和抗CD86 mAb联合使用。短疗程的mAb诱导与西罗莫司联合使用可有效延长同种异体移植物存活时间。
