Journal
INTEGRATIVE BIOLOGY
Volume 5, Issue 1, Pages 231-238Publisher
OXFORD UNIV PRESS
DOI: 10.1039/c2ib20093g
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Funding
- Cancer Center Core Grant [CA16672, CA124782, CA120956, CA141303, CA116127, CA148600]
- Albert J. Ward Foundation
- Alliance for NanoHealth [W81XWH-09-02-0139, W81XWH-10-02-0125]
- Cancer Prevention and Research Institute of Texas
- Center for Transport Oncophysics - Physical Science Oncology Center at The Methodist Hospital Research Institute [U54CA 143837]
- Department of Defense
- Burroughs Wellcome Fund
- CLL Global Research Foundation
- Gillson Longenbaugh Foundation
- Harry T. Mangurian, Jr., Fund for Leukemia Immunotherapy
- Institute of Personalized Cancer Therapy
- Leukemia and Lymphoma Society
- Lymphoma Research Foundation
- Miller Foundation
- National Foundation for Cancer Research
- Pediatric Cancer Research Foundation
- Production Assistance for Cellular Therapies
- Sister Institution Network Fund
- William Lawrence and Blanche Hughes Children's Foundation
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Adoptive transfer of primary T cells genetically modified to have desired specificity can exert an anti-tumor response in some patients. To improve our understanding of their therapeutic potential we have developed a clinically-appealing approach to reveal their in vivo biodistribution using nanoparticles that serve as a radiotracer for imaging by positron emission tomography (PET). T cells electroporated with DNA plasmids from the Sleeping Beauty transposon-transposase system to co-express a chimeric antigen receptor (CAR) specific for CD19 and Firefly luciferase (ffLuc) were propagated on CD19(+) K562-derived artificial antigen presenting cells. The approach to generating our clinical-grade CAR(+) T cells was adapted for electro-transfer of gold nanoparticles (GNPs) functionalized with Cu-64(2+) using the macrocyclic chelator (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid, DOTA) and polyethyleneglycol (GNP-Cu-64/PEG2000). MicroPET/CT was used to visualize CAR(+)EGFPffLucHyTK(+)GNP-Cu-64/PEG2000(+) T cells and correlated with bioluminescence imaging. These data demonstrate that GNPs conjugated with Cu-64(2+) can be prepared as a radiotracer for PET and used to image T cells using an approach that has translational implications.
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