CALCINEURIN INHIBITOR SPARING IN KIDNEY TRANSPLANTATION (CN-01)

肾移植中保留钙调磷酸酶抑制剂 (CN-01)

• 批准号: 7607237
• 负责人: WILLIAM E. HARMON
• 金额: $ 0.14万
• 依托单位: BOSTON CHILDREN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-04-01 至 2008-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7607237
• 关键词: Antigens; Cadaver; Calcineurin inhibitor; Caring; Cell Death; Childhood; Chronic rejection of renal transplant; Computer Retrieval of Information on Scientific Projects Database; Donor person; Dose; Exposure to; Funding; Grant; Immunologic Monitoring; Immunosuppression; Immunosuppressive Agents; Institution; Kidney Transplantation; Lead; Living Donors; Maintenance; Monoclonal Antibodies; Morbidity - disease rate; Outcome; Patients; Pharmaceutical Preparations; Pilot Projects; Protocols documentation; Research; Research Personnel; Resources; Sirolimus; Source; T-Lymphocyte; Therapeutic immunosuppression; Transfusion; Transplantation; United States National Institutes of Health; Week; base; day; design; inhibitor/antagonist; pre-clinical

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Improvements in post transplant care and immunosuppression have led to increasingly successful short-term outcome in pediatric recipients of kidney transplants. Unfortunately, morbidity associated with immunosuppressive agents is substantial and some of these drugs may accelerate chronic allograft nephropathy. The investigators propose that the use of the TOR-inhibitor, sirolimus, will obviate the need for calcineurin inhibitors in post-transplant immunosuppression in recipients of living donor grafts. If this pilot study is successful, the investigators will extend the protocol to include cadaver donor recipients and to a protocol including pre-transplant donor specific transfusions (DST) under sirolimus coverage. This deliberate pre-transplant exposure to donor antigen may lead to donor-immunosuppression even further. This long-term proposal is based on preclinical observations that DST plus T-cell costimulatory blockage (rapamycin) may result in activation induced cell death (AICD) of alloreactive T cells that are harmful to the graft. These protocols will include intense immunologic monitoring which is designed to uncover anti-donor responsiveness as early as possible. Patients will receive humanized anti-CD25 monoclonal antibody Dacluzimab, administered in 5 doses over a 2 month period. The first dose will be administered intra-operatively and the subsequent doses will be administered every two weeks up to 8 weeks post transplantation. Maintenance immunosuppression will also be administered beginning on Day -1.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 移植后护理和免疫抑制的改善导致肾脏移植的儿科接受者的短期结局越来越成功。 不幸的是，与免疫抑制剂相关的发病率很高，其中一些药物可能会加速同种异体移植肾病。 研究人员建议，使用TOR抑制剂Sirolimus将消除在活体供体移植物接受者中移植后免疫抑制中钙调神经磷酸酶抑制剂的需求。 如果这项试验研究成功，研究人员将将协议扩展到包括尸体供体接受者以及在西罗莫司覆盖范围内的协议中，包括移植前捐赠者特定的输血（DST）。 这种故意的移植前接触供体抗原可能会进一步导致供体免疫抑制。 这项长期建议基于临床前观察结果，即DST加T细胞共刺激阻塞（Rapamycin）可能导致激活引起对移植有害的同种反应性T细胞的细胞死亡（AICD）。 这些方案将包括强烈的免疫监测，旨在尽早发现反唐反应性。 患者将接受人源化的抗CD25单克隆抗体Dacluzimab，在2个月内以5剂施用。 第一个剂量将进行术中施用，随后的剂量将在移植后每两周服用每两周一次。 维护免疫抑制也将从第一天开始进行。