CTLA4 IG RENAL ALLOGRAFT SURVIVAL:MAINTENANCE TRTMENT:CYCLOSPORINE & PREDNISONE

CTLA4 IG 同种异体移植肾存活：维持治疗：环孢菌素

• 批准号: 2711852
• 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/2711852
• 关键词: Mammalia; Primates; biological products; drug screening /evaluation; immunology; lymphatic system; surgery; transplantation; urinary tract

Optimal inhibition of the immune response to destroy transplanted organs in clinical transplantation has yet to be achieved. Therefore, transplant recipient patients continue to experience problems with rejection of their transplants as well as the side effects of the non-specific immunosuppressive strategies which are required to maintain these transplants which include an increased incidence of both infections and malignancies. T lymphocytes play an important role in transplant rejection. The B7/CD28 signaling pathway has been shown to be important for effective T cell activation. Previous studies in rodent models have demonstrated that blockade of this pathway with a reagent called CTLA4-Ig can effectively prolong the survival of transplanted organs. The aim of this study was to test the hypothesis that CTLA4-Ig will prolong the survival of renal transplants in a nonhuman primate model. The demonstration of this effect would facilitate the application of this reagen t to prevent graft rejection in clinical transplantation. Renal transplants were performed in rhesus macaques to test 3 specific CTLA4-Ig treatment protocols. 1) CTLA4-Ig alone initiated at the time of transplant; 2) CTLA4-Ig alone initiated 2 days after transplant; and 3) CTLA4-Ig combined with cyclosporine and prednisone initiated at the time of transplants. The results to date indicate that a short course of CTLA4-Ig treatment alone at the time of transplant was associated with marked prolongation of allograft survival in one of four recipients. Delaying the initiation of CTLA4-Ig treatment did not appear to improve survival. A 16-day course of CTLA4-Ig combined with cyclosporine and prednisone prolonged renal allograft survival but not indefinitely. Extension of this triple immunosuppressive therapy to 13 weeks after transplant was associated with increased survival. In summary, CTLA4-Ig is immunosuppressive in the nonhuman primate renal allograft model.

最佳抑制免疫反应破坏移植 器官的临床移植还有待实现。 因此，我们认为， 接受移植的患者继续经历以下问题 他们的移植排斥反应以及 需要非特异性免疫抑制策略 维持这些移植，其中包括增加的发病率 感染和恶性肿瘤。 T淋巴细胞发挥着重要的 在移植排斥中的作用 B7/CD 28信号通路已被证实是 显示对于有效的T细胞活化是重要的。 先前 在啮齿动物模型中的研究表明， 一种名为CTLA 4-IG的试剂可以有效地延长 移植器官的存活。 这项研究的目的是测试 CTLA 4-IG可延长肾移植患者的生存期， 在非人类灵长类动物模型中进行移植。 这个演示 这种作用将有助于应用这种试剂来预防 临床移植中的移植物排斥反应。 肾移植是 在恒河猴中进行，以测试3种特异性CTLA 4-IG治疗 协议. 1)在移植时开始单独使用CTLA 4-IG; 2） 在移植后2天开始单独的CTLA 4-IG;和3）CTLA 4-IG 联合环孢素和泼尼松开始时， 移植 迄今为止的结果表明， 在移植时单独使用CTLA 4-IG治疗与 4例受者中有1例移植物存活时间明显延长。 延迟CTLA 4-IG治疗的开始似乎并不 提高生存率。 CTLA 4-IG联合16天疗程 环孢素和强的松延长移植肾存活， 无限期 将这种三联免疫抑制疗法扩展至 移植后13周与生存率增加相关。 在 总之，CTLA 4-IG在非人灵长类动物肾脏中具有免疫抑制作用， 同种异体移植模型