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 #
5P01CA065493-18
Application #
8379419
Study Section
Special Emphasis Panel (ZCA1-RPRB-J)
Project Start
Project End
Budget Start
2012-07-01
Budget End
2013-06-30
Support Year
18
Fiscal Year
2012
Total Cost
$347,714
Indirect Cost
$103,671
Name
University of Minnesota Twin Cities
Department
Type
DUNS #
555917996
City
Minneapolis
State
MN
Country
United States
Zip Code
55455
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Kean, Leslie S; Turka, Laurence A; Blazar, Bruce R (2017) Advances in targeting co-inhibitory and co-stimulatory pathways in transplantation settings: the Yin to the Yang of cancer immunotherapy. Immunol Rev 276:192-212
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Pourhassan, H; DeFor, T; Trottier, B et al. (2017) MDS disease characteristics, not donor source, predict hematopoietic stem cell transplant outcomes. Bone Marrow Transplant 52:532-538
Kamphorst, Alice O; Wieland, Andreas; Nasti, Tahseen et al. (2017) Rescue of exhausted CD8 T cells by PD-1-targeted therapies is CD28-dependent. Science 355:1423-1427

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