Transplant Biology and Therapy

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）和通过增强的抗肿瘤治疗的相关细胞疗法 活性，通过限制移植物抗宿主病（GVHD）和增强免疫功能来提高HCT的安全性。 通过加速植入和免疫祖细胞恢复重建，并出口 明尼苏达州的发现，以确定性测试的国家或多中心平台。为了实现这些目标， 该计划将集中在以下目标：1）开发新的细胞疗法，以防止复发后 移植，包括自然杀伤（NK）细胞活化和工程化T和NK的过继转移 2）建立降低移植相关发病率和死亡率的方法，包括造血干细胞移植; 干细胞扩增以加速移植，限制GVHD风险的新策略，以及基于细胞的 干预措施，以加强免疫重建和限制机会性感染的危害;和3）带来 明尼苏达大学设计的有希望的移植进展， 明确的评价。技术性贸易壁垒项目由经验丰富的共同领导人，医学博士约翰瓦格纳和丹尼尔 Weisdorf有39名成员，代表7个部门和4所学校或学院（医学院， 药学院、公共卫生学院、理工学院）。在上一个预算年度， 研究人员得到了国家癌症研究所190万美元的直接费用和500万美元的资助。 所有同行审查来源的直接费用为100万美元。自2013年以来，计划成员已出版865本 论文（16%在高影响力期刊上），其中34%来自项目内合作，25%来自 项目间合作，84%来自外部合作。自2013年以来，共有194项临床试验 在这一方案领域下开设了临床研究类别，并招收了4083名参与者。 白血病是明尼苏达州儿童死亡的主要原因， MDS/AML高于全国平均水平。我们针对血液恶性肿瘤的转化研究， GVHD直接解决了我们集水区的这些独特的癌症负担。自2013年以来，与共济会 在癌症中心的支持下，我们招募了3名新的研究人员：Frank Cicarniki博士; Shernan Holtan医学博士; Armin Rashidi医学博士，哲学博士。每个人都有不同的技能和研究重点，并将加强目标的 TBT方案。此外，共济会癌症中心已投资25万美元，用于9个试点项目， 该计划的成员。在这个项目中取得的科学进步构成了我们第一个科学计划的基础。 优先增长-扩大免疫疗法和细胞疗法的最新发现，包括实体瘤 （SPG1）。虽然TBT项目的重点一直是恶性血液病，但其原理、技术 这些方法现在正被应用于实体瘤。

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.