Amer M Najjar1, Pallavi R Manuri2, Simon Olivares1, Leo Flores3, Tiejuan Mi1, Helen Huls1, Elizabeth J Shpall4, Richard E Champlin4, Nashaat Turkman5, Vincenzo Paolillo6, Jason Roszik2, Brian Rabinovich1, Dean A Lee1,7, Mian Alauddin3, Juri Gelovani5, Laurence J N Cooper8,9. 1. Division of Pediatrics, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA. 2. Melanoma Medical Oncology-Research, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA. 3. Department of Cancer Systems Imaging, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA. 4. Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA. 5. Molecular Imaging Program, Karmanos Cancer Institute, Wayne State University, Detroit, MI, USA. 6. Center for Advanced Biomedical Imaging, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA. 7. The University of Texas Graduate School of Biomedical Sciences, Houston, TX, USA. 8. Division of Pediatrics, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA. ljncooper@mdanderson.org. 9. Ziopharm 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-β-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.
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-1thymidine 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-β-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.
Entities:
Keywords:
B cell malignancy; Chimeric antigen receptor; Immunotherapy
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