Preserving Renal Function & Protective Immunity Via Anti-LFA1-Based CNI Avoidance

保护肾功能

基本信息

  • 批准号:
    7736973
  • 负责人:
  • 金额:
    $ 211.26万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2009
  • 资助国家:
    美国
  • 起止时间:
    2009-09-25 至 2014-08-31
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): Despite continued reductions in short-term rejection rates, long-term outcomes have not significantly improved in the past decade. In the face of this the pressing unmet need, there have been no fundamentally new immunosuppressive agents that have been approved in the new millennium. Our Collaborative will investigate efalizumab as an alternative to CNI-based immunosuppression (IS) in kidney and liver transplantation. Clinical endpoints include efficacy and safety and the trial will systematically assess whether avoidance of CNI-based maintenance IS with efalizumab provides superior preservation of renal structure and function and lower rates of PTDM, hypertension, and dyslipidemia relative to a tacrolimus-based regimen. The studies will be heavily leveraged to gain mechanistic insight regarding the etiology of native renal injury and IFTA and to develop proteomic or gene expression biomarkers of progressive renal injury. We will develop clinically relevant, mechanistically based, non-invasive assays for the early detection of renal injury with the goal of translating our findings into practical tools aiding the clinician in patient care. We will acquire important data on the impact of efalizumab and tacrolimus on protective immunity by systematically defining the type and pattern of viral reactivation observed with each regimen, as well as assessing the impact on peripheral lymphocyte homeostasis and the phenotype and function of virus-specific memory T cells. We will determine whether ongoing exposure of the recipient to donor-antigens under the sustained blockade of LFA-1 with efalizumab while avoiding CNI will result in alterations in anti-donor T cell and/or humoral immunity or an Increased Incidence of recently described tolerance signatures. Given the prevalence of renal injury (native and allograft) and centrality of immune function across all transplant settings regardless of IS regimen, we anticipate broad applicability of these goals. We have aligned three high volume transplant hospitals with extensive experience in clinical transplant studies and recruited investigators with substantial, published experience in human transplant immunobiology to insure that our studies will yield clinically meaningful and mechanistically important results. RELEVANCE: Despite reductions in short-term rejection rates, long-term outcomes have not significantly improved in the past decade and there have been no fundamentally new immunosuppressive agents that have been approved in the new millennium. Our Collaborative will investigate efalizumab as an alternative to CNI-based immunosuppression in kidney and liver transplantation.
描述(由申请人提供):尽管短期拒绝率持续下降,但在过去十年中,长期结果并未显着改善。面对这一迫切的未满足的需求,在新的千年里还没有新的免疫抑制剂被批准。我们的合作将研究依法利珠单抗作为替代CNI为基础的免疫抑制(IS)在肾脏和肝脏移植。临床终点包括疗效和安全性,试验将系统评估与基于他克莫司的方案相比,使用依法利珠单抗避免基于CNI的维持IS是否可提供上级肾脏结构和功能保护以及较低的PTDM、高血压和血脂异常发生率。这些研究将被大量利用,以获得关于天然肾损伤和IFTA的病因学的机制见解,并开发进行性肾损伤的蛋白质组学或基因表达生物标志物。我们将开发临床相关的,基于机械的,非侵入性的检测方法,用于早期检测肾损伤,目的是将我们的发现转化为实用工具,帮助临床医生进行患者护理。我们将通过系统地定义每种方案观察到的病毒再活化的类型和模式,以及评估对外周淋巴细胞稳态和病毒特异性记忆T细胞的表型和功能的影响,获得关于依法利珠单抗和他克莫司对保护性免疫的影响的重要数据。我们将确定接受者在依法利珠单抗持续阻断LFA-1的情况下持续暴露于供体抗原,同时避免CNI是否会导致抗供体T细胞和/或体液免疫的改变或最近描述的耐受性特征的发生率增加。考虑到肾损伤(自体肾和同种异体肾)的患病率和免疫功能在所有移植环境中的中心地位,无论IS方案如何,我们预计这些目标具有广泛的适用性。我们已经将三家在临床移植研究方面具有丰富经验的大容量移植医院联系起来,并招募了在人类移植免疫生物学方面具有大量已发表经验的研究人员,以确保我们的研究将产生具有临床意义和机械重要性的结果。 相关性:尽管短期排斥率有所降低,但在过去十年中,长期结果并未显着改善,并且在新千年中尚未批准新的免疫抑制剂。我们的合作将研究依法利珠单抗作为替代CNI为基础的免疫抑制在肾脏和肝脏移植。

项目成果

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CHRISTIAN P LARSEN其他文献

CHRISTIAN P LARSEN的其他文献

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{{ truncateString('CHRISTIAN P LARSEN', 18)}}的其他基金

Admin-Core-001
管理核心-001
  • 批准号:
    10609608
  • 财政年份:
    2022
  • 资助金额:
    $ 211.26万
  • 项目类别:
Transplant Tolerance in Non-Human Primates
非人类灵长类动物的移植耐受性
  • 批准号:
    10518465
  • 财政年份:
    2022
  • 资助金额:
    $ 211.26万
  • 项目类别:
Core-001
核心001
  • 批准号:
    10609609
  • 财政年份:
    2022
  • 资助金额:
    $ 211.26万
  • 项目类别:
Cellular Strategies for Tolerance Induction
耐受诱导的细胞策略
  • 批准号:
    10609610
  • 财政年份:
    2022
  • 资助金额:
    $ 211.26万
  • 项目类别:
Third Generation Costimulation Blockade-Based Tolerance Strategies
第三代基于共刺激封锁的耐受策略
  • 批准号:
    8705983
  • 财政年份:
    2014
  • 资助金额:
    $ 211.26万
  • 项目类别:
TRANSPLANT TOLERANCE IN NONHUMAN PRIMATES
非人类灵长类动物的移植耐受性
  • 批准号:
    8357393
  • 财政年份:
    2011
  • 资助金额:
    $ 211.26万
  • 项目类别:
TRANSLATIONAL STRATEGIES FOR PANCREATIC ISLET XENOTRANSPLANTATION IN NHP
NHP 胰岛异种移植的翻译策略
  • 批准号:
    8357464
  • 财政年份:
    2011
  • 资助金额:
    $ 211.26万
  • 项目类别:
OPTIMIZING IMMUNOTHERAPY FOR ALLOGENEIC ISLET TRANSPLANTATION IN NHP
优化 NHP 异体胰岛移植的免疫治疗
  • 批准号:
    8357444
  • 财政年份:
    2011
  • 资助金额:
    $ 211.26万
  • 项目类别:
TRANSLATIONAL STRATEGIES FOR PANCREATIC ISLET XENOTRANSPLANTATION IN NHP
NHP 胰岛异种移植的翻译策略
  • 批准号:
    8172418
  • 财政年份:
    2010
  • 资助金额:
    $ 211.26万
  • 项目类别:
TRANSPLANT TOLERANCE IN NONHUMAN PRIMATES
非人类灵长类动物的移植耐受性
  • 批准号:
    8172322
  • 财政年份:
    2010
  • 资助金额:
    $ 211.26万
  • 项目类别:

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  • 批准号:
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  • 财政年份:
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  • 资助金额:
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