The Imaging Core is an integral component of this Program Project and will conduct all of the in vivo imaging studies in experimental animal models. The main objective of using non-invasive molecular-genetic imaging in this Program Project is to assess the spatial and temporal dynamics of stem cell trafficking and engraftment, as well as T cell trafficking and lymphoid and myeloid tumor cell targeting. The Imaging Core will utilize several dedicated pre-clinical and clinical imaging instruments, including: bioluminescence imaging (BLI) system, pre-clinical micro-PET/CT for imaging in mice, clinical PET/CT system for imaging non-human primates, Radiochemistry Facilitiy, and Reporter Vecotr Laboraotury of the Dept. of Experimental Diagnostic Imaging (EDI), UT-MDACC. Specifically, for Project 1, the Core will perform repetitive imaging studies to compare spatial-temporal dynamics of engraftment: a) in NOG/SCID mice of two different human cord blood-derived CD34+ hematopoietic stem cell populations (CB-HSC) differentially labeled with FLuc and RLuc reporter genes for BLI: 1) CB-HSC from two unmanipulated cords; 2) unmanipulated vs in vitro expanded CB-HSC, and 3) CB-HSC unmanipulated and expanded with/without fucosylation to improve homing to the bone marrow. For Project III, the Core will perform: a) BLI and 18F-FEAU microPET/CT in NOG/SCID mice to assess spatial-temporal dynamics of trafficking of HSV1-tk/Luc-labeled CB-derived T cells expressing CD19-specific chimeric antigen receptor (CAR+) and compare to that of the CB-derived tri-virus-specific (CD19)CAR+ T cells; b) repetitive PET/CT with 18F-FEAU in rhesus macaques to non-invasively monitor the trafficking and homing of adoptively transferred autologous T lymphocytes expressing HSV1-tk reporter gene and CD19-specific or CD20-specific CARs. For Project IV, the Core will use BLI and microPET/CT to assess the distribution, expansion, and persistence in mice of (1) human AML labeled with RLuc/RFP reporter, (2) high affinity PR1-CTL, and (3) low affinity PR1-CTL labeled with HSVI-tk/FLuc reporter gene. In summary, BLI will enable cost-effective high-throughput studies in mice, while 18F-FEAU PET/CT in mice and nonhuman primates will facilitate transition of the proposed cellular therapies into the clinic.

Public Health Relevance

The Imaging Core is an integral component of this Program Project and will conduct all of the in vivo imaging studies in experimental animal models. The main objective of using non-invasive molecular-genetic imaging in this Program Project is to assess the spatial and temporal dynamics of stem cell trafficking and engraftment, as well as T cell trafficking and lymphoid and myeloid tumor cell targeting.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
5P01CA148600-02
Application #
8555389
Study Section
Special Emphasis Panel (ZCA1-RPRB-J (J1))
Project Start
2011-09-22
Project End
2016-08-31
Budget Start
2012-09-17
Budget End
2013-08-31
Support Year
2
Fiscal Year
2012
Total Cost
$185,519
Indirect Cost
$37,924
Name
University of Texas MD Anderson Cancer Center
Department
Type
DUNS #
800772139
City
Houston
State
TX
Country
United States
Zip Code
77030
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Dave, Hema; Luo, Min; Blaney, J W et al. (2017) Toward a Rapid Production of Multivirus-Specific T Cells Targeting BKV, Adenovirus, CMV, and EBV from Umbilical Cord Blood. Mol Ther Methods Clin Dev 5:13-21
Alsuliman, Abdullah; Muftuoglu, Muharrem; Khoder, Ahmad et al. (2017) A subset of virus-specific CD161+ T cells selectively express the multidrug transporter MDR1 and are resistant to chemotherapy in AML. Blood 129:740-758

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