Rebuilding immunity

描述（由申请人提供）：免疫治疗的使用越来越多，导致大量人群免疫功能改变。仅去年一年，全球就进行了45，000例造血干细胞移植（HSCT）。HSCT后的免疫恢复可能需要数年时间。这意味着大量人口易受各种来源的感染。 用于增强免疫重建的一种策略是过继性T细胞疗法。来自最近的I/III期研究的数据证实了用抗原经历的T细胞重建对于在高剂量化疗和干细胞拯救后产生保护性免疫的重要性，所述免疫是多个免疫缺陷的免疫缺陷综合征的主要原因。 骨髓瘤随着细胞疗法变得越来越普遍，输血医学领域完全处于领先地位，可以开发免疫补充方案。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年培训计划旨在使Aqui博士能够发展细胞治疗方面的专业知识，并在设计和实施以患者为导向的研究方面获得经验。 博士Aqui将在Carl June博士的指导下追求她的职业发展。琼博士是 艾布拉姆森家族癌症研究所（AFCRI）转化研究项目主任，开创了T细胞生物学和癌症和HIV感染的过继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各种资源来测试以下中心假设：用抗CD 3/CD 28珠共刺激T细胞的输注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全面评估，包括：1）评估同种异体HSCT后共刺激同种异体T细胞输注的免疫恢复; 2）确定HSCT后共刺激自体T细胞在疫苗应答中的贡献; 3）识别同种异体和自体HSCT中免疫恢复的障碍。这些研究将为开发未来的综合免疫治疗策略提供基础，包括使用共刺激的T细胞，旨在增加移植后的免疫反应性。

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.