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（由申请人提供）：免疫疗法的越来越多的使用导致了大量免疫功能的人群。仅去年，全世界就进行了45,000个造血干细胞移植（HSCT）。 HSCT后的免疫恢复可能需要数年。这代表了很容易受到各种来源感染的人群。 用于增强免疫重建的一种策略是收养T细胞疗法。最近的I/I研究中的数据证实了使用抗原经验丰富的T细胞重建的重要性，以开发高剂量化学疗法后的保护性免疫力和多种干细胞拯救。 骨髓瘤。随着细胞疗法变得越来越普遍，输血药物的领域是完美的，可以带来开发免疫学补充方案。 Aqui博士已经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年培训计划旨在允许Aqui博士在细胞疗法方面发展专业知识，并获得以患者为导向的研究的设计和实施经验。 Aqui博士将在Carl June博士的指导下追求她的职业发展。六月博士是 艾布拉姆森家庭癌症研究所（AFCRI）转化研究计划主任，并开创了T细胞生物学和癌症和艾滋病毒感染的继发性免疫疗法的转化研究。 Aqui博士建议利用AFCRI，病理学系和宾夕法尼亚大学的多样化资源来检验以下中心假设：注入与抗CD3/CD28珠子一起加速的T细胞加速了定量和定性的免疫重新基础。这项研究的具体目的是对免疫恢复动力学的全面评估，其中包括：1）评估同种异体HSCT后具有同种异体T细胞输注后的免疫恢复； 2）确定HSCT后疫苗反应中综合自体T细胞的贡献； 3）确定同种异体和自体HSCT中免疫恢复的障碍。这些研究将为开发未来综合的免疫疗法策略（包括使用综合的T细胞）提供基础，该策略的使用旨在提高移植后的免疫反应性。