Belatacept and sirolimus prolong nonhuman primate islet allograft survival: adverse consequences of concomitant alefacept therapy.
Belatacept and sirolimus prolong nonhuman primate islet allograft survival: adverse consequences of concomitant alefacept therapy.
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DOI：
10.1111/j.1600-6143.2012.04341.x
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发表时间：
2013-02
期刊：
影响因子：
--
通讯作者：
Kirk AD
中科院分区：
文献类型：
--
作者：
Lowe MC;Badell IR;Turner AP;Thompson PW;Leopardi FV;Strobert EA;Larsen CP;Kirk AD
Calcineurin inhibitors (CNI) and steroids are known to promote insulin resistance, and their avoidance after islet transplantation is preferred from a metabolic standpoint. Belatacept, a B7-specific mediator of costimulation blockade (CoB), is clinically indicated as a CNI alternative in renal transplantation, and we have endeavored to develop a clinically translatable, belatacept-based regimen that could obviate the need for both CNIs and steroids. Based on the known synergy between CoB and mTOR inhibition, we studied rhesus monkeys undergoing MHC-mismatched islet allotransplants treated with belatacept and the mTOR inhibitor, sirolimus. To extend prior work on CoB-resistant rejection, some animals also received CD2 blockade with alefacept (LFA3-Ig). Nine rhesus macaques were rendered diabetic with streptozotocin and underwent islet allotransplantation. All received belatacept and sirolimus; six also received alefacept. Belatacept and sirolimus significantly prolonged rejection-free graft survival (median 225 days compared to 8 days in controls receiving basiliximab and sirolimus; p=0.022). The addition of alefacept provided no additional survival benefit, but was associated with Cytomegalovirus reactivation in 4/6 animals. No recipients produced donor-specific alloantibodies. The combination of belatacept and sirolimus successfully prevents islet allograft survival in rhesus monkeys, but induction with alefacept provides no survival benefit and increases the risk of viral reactivation.
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AlefacePT促进了非人类灵长类动物中的共刺激性封锁基于同种异体移植的存活。
影响因子：
82.9
作者：
通讯作者：
--
影响因子：
3.3
作者：
Smelt, M. J.;de Haan, B. J.;de Vos, P.
通讯作者：
de Vos, P.
影响因子：
8.8
作者：
Vincenti, F.;Charpentier, B.;Larsen, C. P.
通讯作者：
Larsen, C. P.
影响因子：
20.3
作者：
Amir, Avital L.;D'Orsogna, Lloyd J. A.;Heemskerk, Mirjam H. M.
通讯作者：
Heemskerk, Mirjam H. M.
DOI：
10.1111/j.1600-6143.2010.03212.x
发表时间：
2010-09
期刊：
American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons
影响因子：
--
作者：
Turgeon NA;Avila JG;Cano JA;Hutchinson JJ;Badell IR;Page AJ;Adams AB;Sears MH;Bowen PH;Kirk AD;Pearson TC;Larsen CP
通讯作者：
Larsen CP