Rebuilding immunity

重建免疫力

• 批准号: 7020398
• 负责人: NICOLE ALYSE AQUI
• 金额: $ 13.3万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-01-01 至 2010-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7020398
• 关键词: T lymphocyte; autologous transplantation; autotransfusion; blood transfusion; blood treatment; clinical research; hematopoietic tissue transplantation; homologous transplantation; human subject; immunomodulators; leukapheresis; passive immunization; patient oriented research; stem cell transplantation; transplantation immunology

DESCRIPTION (provided by applicant): The increasing use of immunotherapy has led to a substantial population of people with altered immunologic function. Last year alone, 45,000 hematopoietic stem cell transplants (HSCTs) were performed worldwide. Immune recovery following HSCT can take years. This represents a significant population of people vulnerable to infection from a variety of sources. One strategy used to enhance immune reconstitution is adoptive T cell therapy. Data from a recent phase I/I I study confirms the importance of reconstitution with antigen experienced T cells for the development of protective immunity after high dose chemotherapy and stem cell rescue for multiple myeloma. As cellular therapy becomes more commonplace, the field of transfusion medicine is perfectly positioned to take the lead in developing protocols for immunologic repletion. Dr. Aqui has completed residency training in clinical pathology and is currently a Transfusion Medicine fellow at the University of Pennsylvania. The proposed 5 year training program is designed to allow Dr. Aqui to develop expertise in cellular therapy and gain experience in the design and implementation of patient-oriented research. Dr. Aqui will pursue her career development under the mentorship of Dr. Carl June. Dr. June is the Director of the Translational Research Program of the Abramson Family Cancer Research Institute (AFCRI), and has pioneered translational research in T cell biology and adoptive immunotherapy of cancer and HIV infection. Dr. Aqui proposes to use the diverse resources of the AFCRI, the Department of Pathology, and the University of Pennsylvania to test the following central hypothesis: infusion of T cells costimulated with anti-CD3/CD28 beads accelerates quantitative and qualitative immune reconstitution. The specific aims of this study are provide a comprehensive assessment of immune recovery kinetics, which include: 1) evaluating immunological recovery after allogeneic HSCT with costimulated allogeneic T cell infusions; 2) determining the contribution of costimulated autologous T cells in vaccine response after HSCT; and 3) identifying barriers to immune recovery in both allogeneic and autologous HSCT. These studies will provide a foundation on which to develop future integrated immunotherapy strategies, including the use of costimulated T cells, targeted at increasing immune responsiveness in the post-transplant period.

描述(申请人提供)：免疫疗法的使用越来越多，导致了大量免疫功能改变的人。仅去年一年，全球就进行了4.5万例造血干细胞移植。造血干细胞移植后的免疫恢复可能需要数年时间。这代表了大量易受各种来源感染的人。 一种用于促进免疫重建的策略是过继T细胞疗法。最近一项I/I期研究的数据证实，在大剂量化疗和干细胞拯救多发性骨髓瘤后，与经历过抗原的T细胞重建对于发展保护性免疫具有重要意义。 骨髓瘤。随着细胞疗法变得越来越普遍，输血医学领域在开发免疫补充方案方面处于领先地位。阿基博士完成了临床病理学的住院医师培训，目前是宾夕法尼亚大学的输血医学研究员。拟议的5年培训计划旨在让Aqui博士发展细胞治疗方面的专业知识，并在设计和实施以患者为中心的研究方面获得经验。 阿奎博士将在卡尔·琼博士的指导下继续她的职业发展。琼博士是 他是艾布拉姆森家族癌症研究所(AFCRI)翻译研究项目的主任，并在T细胞生物学和癌症和艾滋病毒感染的过继免疫治疗方面开创了翻译研究的先河。阿基博士建议利用AFCRI、病理学系和宾夕法尼亚大学的不同资源来检验以下核心假设：输注带有抗CD3/CD28珠子的共刺激T细胞可以加速定量和定性免疫重建。本研究的具体目的是提供免疫恢复动力学的综合评估，包括：1)评估共刺激同种异体T细胞输注异基因HSCT后的免疫恢复；2)确定共刺激自体T细胞在HSCT后疫苗应答中的作用；3)确定异基因和自体HSCT中免疫恢复的障碍。这些研究将为开发未来的综合免疫治疗策略提供基础，包括使用共刺激T细胞，旨在提高移植后的免疫反应性。