Transplant Biology and Therapy

移植生物学与治疗方案综述 移植生物学和治疗(TBT)计划的科学目标是提高 加强抗肿瘤的造血细胞移植及相关细胞治疗 活性，通过限制移植物抗宿主病(GVHD)和增强免疫来提高HCT的安全性 通过加速植入和免疫祖细胞恢复进行重建，并输出 将明尼苏达州的发现送到国家或多中心平台进行最终测试。为了实现这些目标， 该计划将集中于以下目标：1)开发新的细胞疗法，以防止复发 移植，包括自然杀伤(NK)细胞激活和过继转移工程T细胞和NK细胞 细胞；2)建立减少移植相关发病率和死亡率的方法，包括造血 干细胞扩增加速植入，限制GVHD风险的新策略，以及基于细胞的 加强免疫重建和限制机会性感染危险的干预措施；以及3)带来 明尼苏达大学设计的有望用于国家临床试验的移植进展 明确的评估。TBT计划由经验丰富的联合领导人约翰·瓦格纳和丹尼尔领导 Weisdorf有39名成员，代表7个系和4所学校或学院(医学院、 药学院、公共卫生学院、科学与工程学院)。在上一个预算年度， 研究成员得到了国家癌症研究所190万美元的直接费用和500万美元的支持 来自所有同行审查来源的直接成本为100万美元。自2013年以来，计划成员已经发布了865份 论文(16%在高影响力期刊上)，其中34%来自计划内合作，25%来自 方案间协作，84%来自外部协作。自2013年以来，共有194项临床试验 在这一规划领域下开设了临床研究类别，并招募了4083名参与者。 白血病是明尼苏达州儿童的主要死因，明尼苏达州儿童白血病的发病率较高 MDS/AML高于全国平均水平。我们针对血液系统恶性肿瘤的翻译研究 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 为了支持癌症中心，我们招募了3名新的调查人员：Frank Cichocki博士；Shernan Holtan医学博士；以及 阿明·拉希迪医学博士。每个人都有不同的技能和研究重点，并将增强 TBT计划。此外，共济会癌症中心已投资250,000美元在9个试点项目中授予 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研究的基础 优先发展-扩大免疫疗法和细胞疗法的最新发现，将实体瘤包括在内 (SPG1)。虽然TBT计划的重点一直是血液系统恶性肿瘤，但原则、技术、 而现在，这种方法正在转化为实体肿瘤。

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.