IDEC-131 (anti-CD154), sirolimus and donor-specific transfusion facilitate operational tolerance in non-human primates
IDEC-131 (anti-CD154), sirolimus and donor-specific transfusion facilitate operational tolerance in non-human primates
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DOI：
10.1111/j.1600-6143.2005.00796.x
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发表时间：
2005-05-01
影响因子：
8.8
通讯作者：
Kirk, AD
中科院分区：
文献类型：
--
作者：
Preston, EH;Xu, H;Kirk, AD
CD 154特异性抗体治疗在许多实验移植模型中预防同种异体移植物排斥反应。然而，抗CD 154的初始临床移植试验令人失望，表明需要尚未确定的辅助治疗。在啮齿动物中，供体抗原（例如，供体输血），或mTOR抑制（例如，西罗莫司）增强抗CD 154的功效。我们在主要组织相容性复合体（MHC）不匹配的恒河猴中进行了肾移植，并使用CD 154特异性抗体IDEC- 131和/或西罗莫司和/或移植前供体特异性输血（DST）联合治疗受体。3个月后停止治疗。三联疗法在所有动物中防止了治疗期间的排斥反应，并在五只动物中的三只中导致了手术耐受性，包括在两只受试动物中的供体特异性皮肤移植物接受。IDEC- 131、西罗莫司和DST在预防灵长类动物肾移植排斥反应方面非常有效。这种明显临床适用的方案是有希望的人肾移植试验。
CD154- specific antibody therapy prevents allograft rejection in many experimental transplant models. However, initial clinical transplant trials with anti-CD154 have been disappointing suggesting the need for as of yet undetermined adjuvant therapy. In rodents, donor antigen (e.g., a donor blood transfusion), or mTOR inhibition (e.g., sirolimus), enhances antiCD154 ' s efficacy. We performed renal transplants in major histocompatibility complex-(MHC) mismatched rhesus monkeys and treated recipients with combinations of the CD154- specific antibody IDEC- 131, and/ or sirolimus, and/ or a pre- transplant donor- specific transfusion (DST). Therapy was withdrawn after 3 months. Triple therapy prevented rejection during therapy in all animals and led to operational tolerance in three of five animals including donor- specific skin graft acceptance in the two animals tested. IDEC- 131, sirolimus and DST are highly effective in preventing renal allograft rejection in primates. This apparently clinically applicable regimen is promising for human renal transplant trials.