The aim of this core is to use a xenotransplantation murine model to provide in vivo readouts for experiments proposed in this program project. Specifically, this model will be used for the following purposes: 1. To optimize proliferation and function of T regulatory cells (Treg) for suppression of alloreactive responses. 2. To perform studies testing the hypothesis that human thymocyte progenitor cells (Tprog) will accelerate human thymopoiesis and peripheral blood T cell responses in immunodeficient mice. 3. To optimize proliferation and function of natural killer (NK) cells for leukemia therapy. These data will in turn inform the design of future clinical trials. The core leader will provide valuable knowledge of the stem cell biology, gene manipulations, murine models, and clinical hematopoietic cell transplantation, all relevant to this application. Core D is unique in its capability to allow two of the three Principal Investigators (who do not have access to preclinical murine models;Project 1 and 3) with a critical shared resource to enhance their scientific program.

Public Health Relevance

Our overall goal is to enhance beneficial effects of cord blood transplantation using subpopulations of immune cells for enhanced lympho-hematopoietic recovery in humanized mice. Investigators in Core D will receive T regulatory, T progenitor and NK cells from investigators in Project 1, 2, and 3, respectively, and evaluate them in immunodeficient mice. These in vivo readouts of cord blood hematopoietic stem cells and additional subsets of human cells will then inform the design of clinical trials.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
5P01CA065493-20
Application #
8725958
Study Section
Special Emphasis Panel (ZCA1-RPRB-J)
Project Start
Project End
Budget Start
2014-07-01
Budget End
2015-06-30
Support Year
20
Fiscal Year
2014
Total Cost
$334,331
Indirect Cost
$101,297
Name
University of Minnesota Twin Cities
Department
Type
DUNS #
555917996
City
Minneapolis
State
MN
Country
United States
Zip Code
55455
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Eckfeldt, Craig E; Randall, Nicole; Shanley, Ryan M et al. (2016) Umbilical cord blood transplantation is a suitable option for consolidation of acute myeloid leukemia with FLT3-ITD. Haematologica 101:e348-51
Sarhan, Dhifaf; Cichocki, Frank; Zhang, Bin et al. (2016) Adaptive NK Cells with Low TIGIT Expression Are Inherently Resistant to Myeloid-Derived Suppressor Cells. Cancer Res 76:5696-5706
Pritchett, Joshua C; Green, Jaime S; Thomm, Angela M et al. (2016) CD4+ T Cells Coexpressing CD134 (OX40) Harbor Significantly Increased Levels of Human Herpesvirus 6B DNA Following Umbilical Cord Blood Transplantation. J Infect Dis 214:1911-1915
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Brinkman, C Colin; Iwami, Daiki; Hritzo, Molly K et al. (2016) Treg engage lymphotoxin beta receptor for afferent lymphatic transendothelial migration. Nat Commun 7:12021
Brunstein, Claudio G; Miller, Jeffrey S; McKenna, David H et al. (2016) Umbilical cord blood-derived T regulatory cells to prevent GVHD: kinetics, toxicity profile, and clinical effect. Blood 127:1044-51
Nakamura, Ryotaro; La Rosa, Corinna; Longmate, Jeffrey et al. (2016) Viraemia, immunogenicity, and survival outcomes of cytomegalovirus chimeric epitope vaccine supplemented with PF03512676 (CMVPepVax) in allogeneic haemopoietic stem-cell transplantation: randomised phase 1b trial. Lancet Haematol 3:e87-98
Omer, Aazim K; Weisdorf, Daniel J; Lazaryan, Aleksandr et al. (2016) Late Acute Graft-versus-Host Disease after Allogeneic Hematopoietic Stem Cell Transplantation. Biol Blood Marrow Transplant 22:879-83
Knorr, David A; Wang, Hongbo; Aurora, Mukta et al. (2016) Loss of T Follicular Helper Cells in the Peripheral Blood of Patients with Chronic Graft-versus-Host Disease. Biol Blood Marrow Transplant 22:825-33

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