Rebuilding immunity

越来越多的免疫疗法的使用导致了大量的变态反应患者。 免疫功能。仅去年一年，就进行了45000例造血干细胞移植 全世界。造血干细胞移植后的免疫恢复可能需要数年时间。这代表着相当大的人口数量 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。来自最近一次 I/II期研究证实了与经历过抗原的T细胞重建对 多发性骨髓瘤大剂量化疗及干细胞挽救后保护性免疫的研究进展 骨髓瘤。随着细胞治疗变得越来越普遍，输血医学领域也变得完美起来。 在开发免疫补充方案方面处于领先地位。阿基博士已经完成了 临床病理学住院医师培训，目前是加州大学输血医学研究员 宾夕法尼亚州。拟议的5年培训计划旨在让阿基博士在 并在设计和实施以患者为中心的研究方面积累经验。 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 艾布拉姆森家族癌症研究所(AFCRI)转化研究项目主任， 并在T细胞生物学和癌症和艾滋病毒的过继免疫治疗方面开创了转化研究 感染。阿基博士建议利用AFCRI、病理学系和 宾夕法尼亚大学测试以下中心假说：输注共刺激T细胞 抗CD3/CD28微球可加速定量和定性免疫重建。的具体目标 本研究对免疫恢复动力学进行了全面的评价，包括：1) 共刺激同种异体T细胞输注评估异基因造血干细胞移植后的免疫恢复 确定共刺激的自体T细胞在HSCT后疫苗应答中的作用； 识别异基因和自体造血干细胞移植中免疫恢复的障碍。这些研究将提供 发展未来综合免疫治疗策略的基础，包括使用 共刺激T细胞，旨在提高移植后的免疫反应性。

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) wereperformed 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/II 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 Universityof 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.