Rebuilding immunity

重建免疫力

• 批准号: 7324758
• 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/7324758
• 关键词: 5-(6)-carboxyfluorescein diacetate succinimidyl ester; Adoptive Immunotherapy; Affect; Allogeneic Bone Marrow Transplantation; Allogenic; Antigens; Archives; Autologous; Autologous Transplantation; Biological Assay; CD8B1 gene; Cells; Cellular biology; Clinical Pathology; Clinical Trials; Data; Development; Donor Lymphocyte Infusion; Dose; Emigrant; Evaluation; Family; Foundations; Future; Goals; HIV Infections; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Hematopoietic stem cells; High Dose Chemotherapy; Immune; Immune response; Immunity; Immunization; Immunologic Deficiency Syndromes; Immunologics; Immunotherapy; Infection; Infusion procedures; Kinetics; Knowledge; Lead; Leukocytes; Life; Lymphocyte; Lymphoid; Maximum Tolerated Dose; Medicine; Memory; Mentorship; Methods; Monoclonal Antibody HuM291; Multiple Myeloma; Muromonab-CD3; Output; Pathology; Patients; Pennsylvania; Phase; Phase I Clinical Trials; Population; Positioning Attribute; Production; Protocols documentation; Recovery; Relapse; Research Ethics Committees; Research Institute; Residencies; Resources; Sampling; Secondary to; Source; Speed; Standards of Weights and Measures; Stem cell transplant; Stem cells; Supplementation; T-Cell Development; T-Cell Receptor; T-Lymphocyte; T-Lymphocyte Subsets; Testing; Toxic effect; Training; Training Programs; Transfusion; Translational Research; Transplantation; Universities; Vaccines; anticancer research; cancer immunotherapy; career; cell type; cytokine; design; experience; graft vs host disease; immune function; patient oriented research; programs; reconstitution; response; time use

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.

越来越多地使用免疫疗法已经导致大量患有改变的人， 免疫功能仅去年一年，就进行了45,000例造血干细胞移植（HSCT） 国际吧HSCT后的免疫恢复可能需要数年时间。这代表了一个重要的人口， 易受各种来源感染的人。 用于增强免疫重建的一种策略是过继性T细胞疗法。数据来自最近的 I/II期研究证实了用抗原经历的T细胞重建对于 大剂量化疗和干细胞拯救后保护性免疫的发展 骨髓瘤随着细胞疗法变得越来越普遍，输血医学领域是完美的。 定位于在开发免疫学补充方案方面处于领先地位。阿奎博士已经完成了 临床病理学的住院医师培训，目前是多伦多大学的输血医学研究员。 宾夕法尼亚拟议的5年培训计划旨在让Aqui博士发展以下方面的专业知识： 细胞疗法，并在设计和实施以患者为导向的研究获得经验。 Aqui博士将在Carl June博士的指导下寻求职业发展。琼博士是 艾布拉姆森家庭癌症研究所（AFCRI）转化研究项目主任， 并在T细胞生物学和癌症及艾滋病毒过继免疫疗法方面开创了转化研究 感染Aqui博士建议利用AFCRI，病理学系的各种资源， 宾夕法尼亚大学测试以下中心假设：输注T细胞与 抗CD 3/CD 28珠粒加速定量和定性免疫重建。的具体目标 本研究提供了免疫恢复动力学综合评估，包括：1） 评估在具有共刺激的同种异体T细胞输注的同种异体HSCT后的免疫恢复; 2） 确定HSCT后共刺激的自体T细胞在疫苗应答中的贡献;和3） 识别同种异体和自体HSCT中免疫恢复的障碍。这些研究将提供 一个基础上，开发未来的综合免疫治疗策略，包括使用 共刺激的T细胞，旨在增加移植后的免疫反应性。