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.