MARROW TRANSPLANT IN CANCER THERAPY--T-CELL RECOVERY

癌症治疗中的骨髓移植——T 细胞恢复

• 批准号: 2733038
• 负责人: JULIA L HURWITZ
• 金额: $ 12.87万
• 依托单位: ST. JUDE CHILDREN'S RESEARCH HOSPITAL
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-08-01 至 1999-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2733038
• 关键词: CD antigens; MHC class II antigen; SCID mouse; T lymphocyte; bone marrow transplantation; clinical research; cytokine receptors; flow cytometry; gene expression; graft versus host disease; histocompatibility; histocompatibility typing; homologous transplantation; human subject; human therapy evaluation; interleukin 2; neoplasm /cancer immunotherapy; neoplasm /cancer therapy; postoperative complications; receptor expression; vaccinia virus; virus antigen; virus infection mechanism

This is a Shannon award providing partial support for the research projects that fall short of the assigned Institute's funding range but are in the margin of excellence. The Shannon award is intended to provide support to test the feasibility of the approach; develop further tests and refine research techniques; perform secondary analysis of available data sets; or conduct discrete projects that can demonstrate the PI's research capabilities or lend additional weight to an already meritorious application. The abstract below is taken from the original document submitted by the principal investigator. DESCRIPTION: (Applicant's Abstract) The applicant's overall aim is to reduce the risk of lethal virus infections that endanger patients after BMT. Particularly deadly is the lymphoproliferative disease caused by EBV. In promising clinical trials at St. Jude's Children's Research Hospital, BMT recipients are receiving EBV-specific memory T cells derived from the marrow donor. Despite favorable preliminary results, three potential problems remain. The problems will be resolved as follows: 1) virus-specific memory T cells may cause graft-versus-host disease. No method has been designed to remove host reactive cells from the donor T cells. The method will be perfected and examined by in vitro testing to ensure that treated cells retain full virus-specific activity. 2) Memory T cells depleted of host reactive cells may lose the capacity to persist and function in vivo. The function of T cells depleted of host reactive cells will be tested in vivo by the use of mouse models. Priming protocols will be designed to optimize virus specific memory T cell activity. 3) Patients may be infected by virulent laboratory stock viruses currently used to expand the virus specific memory T cells in vitro. Protocols will be designed that utilize EBV peptides rather than live virus for T cell stimulations. Individuals from nonminority ethnic groups are already eligible for peptide-based immunotherapeutic programs because their MHC antigens and associated EBV peptides have been studied. To broaden the applicability of peptide-based immunotherapy, the EBV peptides appropriate for T cell triggering in minority/ethnic groups will be defined. BMT is not a routine cancer treatment in many centers, but the risk of serious viral complications remains high.

这是香农奖，为研究提供部分支持 未达到指定研究所资助范围但 处于卓越的边缘。香农奖旨在提供 支持测试该方法的可行性；开发进一步的测试 并完善研究技术；对可用的进行二次分析 数据集；或开展可以展示 PI 的离散项目 研究能力或对已经有功绩的人给予额外的重视 应用。以下摘要摘自原始文件 由主要研究者提交。 描述：（申请人的摘要）申请人的总体目标是 降低感染后危及患者的致命病毒感染的风险 骨髓移植。尤其致命的是由以下原因引起的淋巴增殖性疾病： EB病毒。圣裘德儿童研究中心进行的临床试验充满希望 医院、BMT 接受者正在接受 EBV 特异性记忆 T 细胞 来自骨髓捐赠者。尽管初步结果良好， 仍然存在三个潜在问题。问题将解决如下 如下：1）病毒特异性记忆T细胞可能引起移植物抗宿主 疾病。尚未设计出任何方法来去除宿主反应性细胞 供体 T 细胞。该方法将由 in 来完善和检验 体外测试以确保处理过的细胞保留完整的病毒特异性 活动。 2) 宿主反应性细胞耗尽的记忆 T 细胞可能会失去 在体内持续存在和发挥作用的能力。 T细胞的功能 耗尽宿主反应细胞将通过使用进行体内测试 鼠标模型。启动方案将旨在优化病毒 特定记忆 T 细胞活性。 3）患者可能被感染 目前用于扩增病毒的剧毒实验室库存病毒 体外特异性记忆T细胞。协议将被设计为 利用 EBV 肽而不是活病毒来刺激 T 细胞。 来自非少数民族群体的个人已经有资格获得 基于肽的免疫治疗方案，因为它们的 MHC 抗原和 相关的 EBV 肽已被研究。扩大适用范围 基于肽的免疫疗法，适合T细胞的EBV肽 将定义少数民族/族裔群体的触发。 BMT 不是 许多中心都进行常规癌症治疗，但存在严重病毒感染的风险 并发症仍然很高。