Gene and Cytokine Expression in Tolerance and GVHD
耐受性和 GVHD 中的基因和细胞因子表达
基本信息
- 批准号:7770988
- 负责人:
- 金额:$ 40万
- 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 2013-08-31
- 项目状态:已结题
- 来源:
- 关键词:AntithymoglobulinB-LymphocytesBiological AssayBone MarrowCD4 Positive T LymphocytesCancer PatientCell TransplantationCell TransplantsCellsChimerismClinical ResearchClinical TreatmentClinical TrialsCross-Sectional StudiesCyclosporineCyclosporinsCytokine GeneDendritic CellsDevelopmentDrug usageEnrollmentFreedomFutureGene ChipsGene ExpressionGenesGoalsGraft RejectionHematopoieticHormonesImmuneImmune ToleranceImmunologic MonitoringImmunosuppressive AgentsInterleukin-10Interleukin-4KidneyKidney TransplantationLymphatic IrradiationLymphomaMaintenanceMolecularMonitorNatural Killer CellsOutcomeParentsPatient MonitoringPatientsPatternPeripheral Blood Mononuclear CellPharmaceutical PreparationsPreventionProceduresProcessProductionResearch DesignSorting - Cell MovementT-LymphocyteT-Lymphocyte SubsetsTimeTransplant RecipientsTransplantationTreatment ProtocolsWithdrawalbasechronic graft versus host diseaseconditioningcytokinedesigndrug withdrawalgraft functiongraft vs host diseaseimprovedinsightleukemia/lymphomamonocytemycophenolate mofetilnovelpatient safetypre-clinicalpreventtumor
项目摘要
DESCRIPTION (provided by applicant): Studies are proposed to enhance and improve the immune monitoring of the peripheral blood mononuclear cells (PBMCs) of patients enrolled in two parent clinical trials; one designed to induce immune tolerance to combined kidney and hematopoietic cell transplants and another designed to prevent graft versus host disease (GVHD) after hematopoietic cell transplantation (HCT) for the treatment of leukemia and lymphoma. The goals of the proposed immune monitoring are to use serial analyses of gene microarrays and patterns of intracellular cytokine production to predict which patients can be safely withdrawn from all immunosuppressive drugs at 6 months after transplantation without the subsequent development of rejection episodes in the case of the kidney transplant patients and without the development of GVHD in the case of the hematolymphoid cancer patients. The gene microarray studies build upon recent cross sectional studies that show a "tolerance" gene expression pattern in kidney transplant patients with good graft function off drugs, and a "GVHD" expression pattern that differentiates patients with and without chronic GVHD. We plan to apply the microarray assays to serial longitudinal monitoring of patients in the two trials. In addition, our preclinical and clinical studies of the monitoring of cytokine production patterns of T cell subsets has delineated an IL-4 and IL-10 increase pattern that is associated with the successful induction of tolerance and prevention of GVHD. We will apply the serial monitoring of the changed cytokine patterns to help guide the safe withdrawal of all immunosuppressive drugs in concert with the gene array studies in the future. In addition to providing information about guidance of drug withdrawal, the studies are designed to provide further insight into the cellular and molecular immune mechanisms of tolerance and GVHD protection.
描述(申请人提供):建议开展两项研究,以加强和改善对参加两项双亲临床试验的患者的外周血单核细胞(PBMC)的免疫监测;一项研究旨在诱导对肾脏和造血细胞联合移植的免疫耐受,另一项研究旨在预防白血病和淋巴瘤的造血细胞移植(HCT)后移植物抗宿主病(GVHD)。拟议的免疫监测的目标是使用基因微阵列和细胞内细胞因子产生模式的系列分析来预测哪些患者可以在移植后6个月安全地停用所有免疫抑制药物,而肾移植患者不会随后发生排斥反应,血淋巴样癌患者不会发生移植物抗宿主病。基因芯片研究建立在最近的横断面研究基础上,这些研究表明,肾移植患者在停药后移植物功能良好的情况下存在“耐受性”基因表达模式,以及区分患有和不患有慢性移植物抗宿主病的患者的“移植物抗宿主病”表达模式。我们计划将微阵列分析应用于两个试验中对患者的连续纵向监测。此外,我们对T细胞亚群细胞因子产生模式的监测的临床前和临床研究描绘了与成功诱导耐受和预防GVHD相关的IL-4和IL-10升高模式。我们将应用变化的细胞因子模式的连续监测,以帮助指导所有免疫抑制药物的安全停用,以配合未来的基因阵列研究。除了提供有关药物停药指导的信息外,这些研究还旨在进一步深入了解耐受和GVHD保护的细胞和分子免疫机制。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
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Robert Lowsky其他文献
Robert Lowsky的其他文献
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{{ truncateString('Robert Lowsky', 18)}}的其他基金
Gene and Cytokine Expression in Tolerance and GVHD
耐受性和 GVHD 中的基因和细胞因子表达
- 批准号:
8319625 - 财政年份:2009
- 资助金额:
$ 40万 - 项目类别:
Gene and Cytokine Expression in Tolerance and GVHD
耐受性和 GVHD 中的基因和细胞因子表达
- 批准号:
7937685 - 财政年份:2009
- 资助金额:
$ 40万 - 项目类别:
Gene and Cytokine Expression in Tolerance and GVHD
耐受性和 GVHD 中的基因和细胞因子表达
- 批准号:
8134262 - 财政年份:2009
- 资助金额:
$ 40万 - 项目类别:
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