and here's the latest wrinkle on ablation with ganciclovir......
Mol Imaging Biol. 2016 Dec;18(6):838-848.
Imaging of Sleeping Beauty-Modified CD19-Specific T Cells Expressing HSV1-Thymidine Kinase by Positron Emission Tomography.
Najjar AM1, Manuri PR2, Olivares S1, Flores L 2nd3, Mi T1, Huls H1, Shpall EJ4, Champlin RE4, Turkman N5, Paolillo V6, Roszik J2, Rabinovich B1, Lee DA1,7, Alauddin M3, Gelovani J5, Cooper LJ8,9.
Author information
1Division of Pediatrics, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.2Melanoma Medical Oncology-Research, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.3Department of Cancer Systems Imaging, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.4Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.5Molecular Imaging Program, Karmanos Cancer Institute, Wayne State University, Detroit, MI, USA.6Center for Advanced Biomedical Imaging, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.7The University of Texas Graduate School of Biomedical Sciences, Houston, TX, USA.8Division of Pediatrics, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA. ljncooper@mdanderson.org.9Ziopharm Oncology Inc., Boston, MA, USA. ljncooper@mdanderson.org.
Abstract
PURPOSE:We have incorporated a positron emission tomography (PET) functionality in T cells expressing a CD19-specific chimeric antigen receptor (CAR) to non-invasively monitor the adoptively transferred cells.
PROCEDURES:We engineered T cells to express CD19-specific CAR, firefly luciferase (ffLuc), and herpes simplex virus type-1 thymidine kinase (TK) using the non-viral-based Sleeping Beauty (SB) transposon/transposase system adapted for human application. Electroporated primary T cells were propagated on CD19+ artificial antigen-presenting cells.
RESULTS:After 4 weeks, 90 % of cultured cells exhibited specific killing of CD19+ targets in vitro, could be ablated by ganciclovir, and were detected in vivo by bioluminescent imaging and PET following injection of 2'-deoxy-2'-[18F]fluoro-5-ethyl-1-ß-D-arabinofuranosyl-uracil ([18F]FEAU).
CONCLUSION:This is the first report demonstrating the use of SB transposition to generate T cells which may be detected using PET laying the foundation for imaging the distribution and trafficking of T cells in patients treated for B cell malignancies. |
