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01-12-2016 | Research Article

Imaging of Sleeping Beauty-Modified CD19-Specific T Cells Expressing HSV1-Thymidine Kinase by Positron Emission Tomography

Authors: Amer M. Najjar, Pallavi R Manuri, Simon Olivares, Leo Flores II, Tiejuan Mi, Helen Huls, Elizabeth J. Shpall, Richard E. Champlin, Nashaat Turkman, Vincenzo Paolillo, Jason Roszik, Brian Rabinovich, Dean A. Lee, Mian Alauddin, Juri Gelovani, Laurence J.N. Cooper

Published in: Molecular Imaging and Biology | Issue 6/2016

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.

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Title: Imaging of Sleeping Beauty-Modified CD19-Specific T Cells Expressing HSV1-Thymidine Kinase by Positron Emission Tomography
Authors: Amer M. Najjar
Pallavi R Manuri
Simon Olivares
Leo Flores II
Tiejuan Mi
Helen Huls
Elizabeth J. Shpall
Richard E. Champlin
Nashaat Turkman
Vincenzo Paolillo
Jason Roszik
Brian Rabinovich
Dean A. Lee
Mian Alauddin
Juri Gelovani
Laurence J.N. Cooper
Publication date: 01-12-2016
Publisher: Springer US
Published in: Molecular Imaging and Biology / Issue 6/2016
Print ISSN: 1536-1632
Electronic ISSN: 1860-2002
DOI: https://doi.org/10.1007/s11307-016-0971-8

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Imaging of Sleeping Beauty-Modified CD19-Specific T Cells Expressing HSV1-Thymidine Kinase by Positron Emission Tomography

Abstract

Purpose

Procedures

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Procedures

Results

Conclusion

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