Transplant Biology and Therapy

移植生物学和治疗

• 批准号: 10333253
• 负责人: John E. Wagner
• 金额: $ 4.85万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-06-01 至 2024-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10333253
• 关键词: AML/MDS; Acute Graft Versus Host Disease; Address; Adoptive Transfer; Adult; Allogenic; Antineoplastic Agents; Area; Award; Biology; Biometry; Blood; Blood Platelets; Bone Marrow Transplantation; Budgets; Cancer Burden; Cancer Center; Cancer Center Support Grant; Catchment Area; Categories; Cause of Death; Cell Therapy; Cells; Child; Childhood; Clinical Research; Clinical Trials; Clinical Trials Network; Collaborations; Complex; Direct Costs; Doctor of Philosophy; Engineering; Engraftment; Enrollment; Evaluation; Flow Cytometry; Genetic; Goals; Grant; Growth; Health; Hematologic Neoplasms; Hematology; Hematopoietic; Hematopoietic stem cells; Homologous Transplantation; Immune; Immunology; Immunotherapy; Incidence; Intervention; Investigation; Journals; Laboratories; Malignant Neoplasms; Medicine; Methods; Minnesota; Modeling; Morbidity - disease rate; Multi-Institutional Clinical Trial; NK Cell Activation; National Cancer Institute; National Heart, Lung, and Blood Institute; Natural Killer Cells; Oncology; Opportunistic Infections; Paper; Participant; Patients; Peer Review; Pharmacy Schools; Physician Executives; Pilot Projects; Play; Population; Pre-Clinical Model; Principal Investigator; Public Health Schools; Publishing; Recovery; Regulatory T-Lymphocyte; Relapse; Research; Research Personnel; Resource Sharing; Risk; Role; Safety; Schools; Science; Scientific Advances and Accomplishments; Services; Solid Neoplasm; Source; Targeted Research; Technology; Testing; Therapeutic; Translating; Translational Research; Transplantation; Umbilical Cord Blood; Universities; Work; base; cancer cell; cancer genomics; college; efficacy testing; experience; first-in-human; graft vs host disease; hazard; hematopoietic cell transplantation; hematopoietic stem cell expansion; immune reconstitution; improved; in vivo; innovation; leukemia; medical schools; member; mortality; neutrophil; novel strategies; pediatric department; preclinical study; prevent; progenitor; programs; recruit; safety testing; skills; success; translational therapeutics

Transplant Biology and Therapy Program Summary The scientific goals of the Transplant Biology and Therapy (TBT) Program are to enhance the efficacy of hematopoietic cell transplantation (HCT) and related cellular therapies through augmented anti-neoplastic activity, improve the safety of HCT by limiting graft-versus-host disease (GVHD) and enhancing immune reconstitution through accelerated engraftment and immune progenitor recovery, and export University of Minnesota discoveries to a national or multicenter platform for definitive testing. To achieve these goals, the Program will focus on the following Aims: 1) to develop new cellular therapeutics to prevent relapse after transplantation, including natural killer (NK) cell activation and the adoptive transfer of engineered T and NK cells; 2) to establish methods for reducing transplant-related morbidity and mortality, including hematopoietic stem cell expansion to accelerate engraftment, novel strategies to limit the risk of GVHD, and cell-based interventions to augment immune reconstitution and limit the hazards of opportunistic infection; and 3) to bring promising transplantation advances devised at the University of Minnesota to national clinical trials for definitive evaluation. The TBT Program is led by experienced co-leaders, MDs John Wagner and Daniel Weisdorf and has 39 members, representing 7 departments and 4 schools or colleges (Medical School, College of Pharmacy, School of Public Health, College of Science and Engineering). For the last budget year, research members were supported by $1.9 million in direct costs from the National Cancer Institute and $5.0 million in direct costs from all peer-reviewed sources. Since 2013, Program members have published 865 papers (16% in high-impact journals), 34% of which resulted from intraprogrammatic collaborations, 25% from interprogrammatic collaborations, and 84% from external collaborations. Since 2013, 194 clinical trials in all clinical research categories have opened under this programmatic area and have enrolled 4083 participants. Leukemia is the leading cause of death for Minnesota's children and Minnesota has a higher incidence of MDS/AML than the national average. Our translational research targeting hematologic malignancies and GVHD directly addresses these unique cancer burdens of our catchment area. Since 2013, with Masonic Cancer Center support, we have recruited 3 new investigators: Frank Cichocki, PhD; Shernan Holtan, MD; and Armin Rashidi MD, PhD. Each has differing skills and research emphasis and will enhance the goals of the TBT Program. Additionally, the Masonic Cancer Center has invested $250,000 in 9 pilot projects awarded to members of the Program. The scientific advances made in this program form the basis for our first Scientific Priority for Growth – expand recent discoveries in immunotherapy and cellular therapies to include solid tumors (SPG1). While the focus of TBT program has been on hematologic malignancies, the principles, technologies, and approaches are now being translated into solid tumors.

移植生物学和治疗计划摘要 移植生物学和治疗（TBT）计划的科学目标是提高 造血细胞移植（HCT）和相关的细胞疗法通过增强的抗肿瘤疗法 活动，通过限制移植物抗宿主病（GVHD）并增强免疫力，提高HCT的安全性 通过加速植入和免疫祖细胞恢复和出口大学重建 明尼苏达州发现了国家或多中心平台进行确定测试。为了实现这些目标， 计划将重点介绍以下目的：1）开发新的蜂窝疗法以防止退休 移植，包括天然杀手（NK）细胞激活和工程T和NK的自适应转移 细胞； 2）建立降低移植相关的发病率和死亡率的方法，包括造血 干细胞扩展以加速植入，限制GVHD风险的新型策略和基于细胞的风险 增加免疫重建的干预措施并限制机会性感染的危害； 3）带来 明尼苏达大学为国家临床试验而设计的有希望的移植进展 确定评估。 TBT计划由经验丰富的共同领导者John Wagner和Daniel领导 韦斯多夫（Weisdorf）和39名成员，代表7个部门和4所学校或大学（医学院， 医学与工程学院公共卫生学院药学院）。在最后一个预算年度， 研究成员得到了国家癌症研究所的190万美元直接成本和5.0美元的支持。 所有经过同行评审的来源的直接成本。自2013年以来，计划成员已发布865 论文（在高影响期刊中为16％），其中34％是由术中合作造成的，25％来自 解释性合作协作，外部协作中有84％。自2013年以来，所有人进行了194个临床试验 临床研究类别已在此程序化领域开放，并招募了4083名参与者。 白血病是明尼苏达州的孩子的主要死亡原因，明尼苏达州的发生率更高 MDS/AML比全国平均水平。我们的翻译研究针对血液学恶性肿瘤和 GVHD直接解决了我们集水区的这些独特的癌症燃烧。自2013年以来，有共济会 癌症中心的支持，我们招募了3名新调查员：弗兰克·塞科奇（Frank Cichocki），博士；医学博士Shernan Holtan；和 Armin Rashidi医学博士，博士。每个人都有不同的技能和研究重点，并将增强 TBT程序。此外，共济会癌症中心已经在9个授予的飞行员项目中投资了25万美元 该计划的成员。该计划的科学进步构成了我们第一次科学的基础 生长的优先级 - 扩大免疫疗法和细胞疗法的最新发现到包括实体瘤 （SPG1）。虽然TBT计划的重点一直放在血液学恶性肿瘤上，但原理，技术， 现在正在将方法转化为实体瘤。