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.
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.
|Sekine, Takuya; Marin, David; Cao, Kai et al. (2016) Specific combinations of donor and recipient KIR-HLA genotypes predict for large differences in outcome after cord blood transplantation. Blood 128:297-312|
|Patel, Shabnum; Lam, Sharon; Cruz, Conrad Russell et al. (2016) Functionally Active HIV-Specific T Cells that Target Gag and Nef Can Be Expanded from Virus-NaÃ¯ve Donors and Target a Range of Viral Epitopes: Implications for a Cure Strategy after Allogeneic Hematopoietic Stem Cell Transplantation. Biol Blood Marrow Transplant 22:536-41|
|Torikai, Hiroki; Mi, Tiejuan; Gragert, Loren et al. (2016) Genetic editing of HLA expression in hematopoietic stem cells to broaden their human application. Sci Rep 6:21757|
|Tripathi, Satyendra C; Peters, Haley L; Taguchi, Ayumu et al. (2016) Immunoproteasome deficiency is a feature of non-small cell lung cancer with a mesenchymal phenotype and is associated with a poor outcome. Proc Natl Acad Sci U S A 113:E1555-64|
|Patel, Shabnum; Jones, R Brad; Nixon, Douglas F et al. (2016) T-cell therapies for HIV: Preclinical successes and current clinical strategies. Cytotherapy 18:931-42|
|Bollard, Catherine M; Heslop, Helen E (2016) T cells for viral infections after allogeneic hematopoietic stem cell transplant. Blood 127:3331-40|
|Thompson, Philip A; Perera, Travis; Marin, David et al. (2016) Double umbilical cord blood transplant is effective therapy for relapsed or refractory Hodgkin lymphoma. Leuk Lymphoma 57:1607-15|
|Naik, Swati; Nicholas, Sarah K; Martinez, Caridad A et al. (2016) Adoptive immunotherapy for primary immunodeficiency disorders with virus-specific T lymphocytes. J Allergy Clin Immunol 137:1498-1505.e1|
|Kebriaei, Partow; Singh, Harjeet; Huls, M Helen et al. (2016) Phase I trials using Sleeping Beauty to generate CD19-specific CAR T cells. J Clin Invest 126:3363-76|
|Spielmann, Guillaume; Bollard, Catherine M; Kunz, Hawley et al. (2016) A single exercise bout enhances the manufacture of viral-specific T-cells from healthy donors: implications for allogeneic adoptive transfer immunotherapy. Sci Rep 6:25852|
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