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.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 移植后护理和免疫抑制的改善使肾移植儿科接受者的短期结果日益成功。 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慢性同种异体移植肾病。 研究人员提出，使用 TOR 抑制剂西罗莫司将消除活体移植受者移植后免疫抑制中钙调神经磷酸酶抑制剂的需要。 如果这项试点研究成功，研究人员将扩大该方案以包括尸体供体接受者，并扩大到包括西罗莫司覆盖下的移植前供体特异性输血（DST）的方案。 这种有意的移植前暴露于供体抗原可能会进一步导致供体免疫抑制。 这一长期提议基于临床前观察，即 DST 加 T 细胞共刺激阻断（雷帕霉素）可能会导致同种异体反应性 T 细胞的激活诱导细胞死亡 (AICD)，对移植物有害。 这些方案将包括严格的免疫监测，旨在尽早发现抗供体反应。 患者将接受人源化抗 CD25 单克隆抗体 Dacluzimab，在 2 个月内分 5 剂给药。 第一剂将在术中注射，随后的剂量将每两周注射一次，直至移植后 8 周。 维持性免疫抑制也将从第-1天开始进行。