CTLA4 IG ON RENAL ALLOGRAFT SURVIVAL: TREATMENT DELAY & COMB W/ CYCLOSPORINE

CTLA4 IG 对同种异体移植肾存活率的影响：治疗延迟

• 批准号: 2711853
• 金额: $ 3.43万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/2711853
• 关键词: Mammalia; Primates; biological products; drug screening /evaluation; immunology; lymphatic system; surgery; transplantation; urinary tract

The aim of this study was to test the hypothesis that CTLA4-Ig will prolong survival of renal allografts in a nonhuman primate model. CTLA4-Ig has been shown to modify the allograft rejection response to produce prolonged graft survival and/or induce specific unresponsiveness in rodent models. Adult rhesus macaques (11.8-13.5 kg) were utilized for these studies. Ten animals received an allogeneic renal transplant, a left nephrectomy and simultaneous right contralateral ureter ligation. The paired transplants were performed simultaneously by exchange of kidneys between recipient individuals. One recipient in each pair was treated with CTLA4-Ig and the other served as a control being treated with human albumin. Renal allografts in the control treatment group promptly fail (4-8 days) and the histologic analysis suggests both a cellular and humoral immune mediated mechanism. CTLA4-Ig treatment in one of four recipients was associated with marked prolongation of allograft su rvival. One CTLA4-Ig treated recipient died secondary to necrosis of the distal transplant ureter and was not included in the analysis. In summary, the results of this pilot study suggest that CTLA4-Ig has the ability to prolong primate renal allograft survival.

这项研究的目的是检验CTLA4-Ig 将延长在非人类灵长类动物模型中移植肾的存活时间。 CTLA4-Ig已被证明可以改变同种异体移植排斥反应 延长移植物存活时间和/或诱导特异性 啮齿动物模型中的无反应。成年恒河猴(11.8-13.5 Kg)用于这些研究。十只动物收到了 同种异体肾移植，左肾切除同时右肾切除 对侧输尿管结扎术。配对的移植手术已经完成 同时通过受赠者之间的肾脏交换。 每对受者中的一人接受CTLA4-Ig治疗，另一人接受CTLA4-Ig治疗 作为人血清白蛋白治疗的对照组。肾 对照组同种异体移植物迅速失效(4-8天)， 组织学分析表明细胞免疫和体液免疫。 中介机制。CTLA4-Ig治疗4例受者中的1例 与同种异体移植物存活时间显著延长有关。一 接受CTLA4-Ig治疗的受者继发于远端坏死 移植输尿管，不包括在分析中。总而言之， 这项初步研究的结果表明CTLA4-Ig具有 以延长灵长类移植肾的存活时间。