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

Amer M. Najjar; Pallavi R. Manuri; Simon Olivares; Leo Flores; 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

doi:10.1007/s11307-016-0971-8

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

Amer M. Najjar, Pallavi R. Manuri, Simon Olivares, Leo Flores, 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

Research output: Contribution to journal › Article › peer-review

21 Scopus citations

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.

Original language	English (US)
Pages (from-to)	838-848
Number of pages	11
Journal	Molecular Imaging and Biology
Volume	18
Issue number	6
DOIs	https://doi.org/10.1007/s11307-016-0971-8
State	Published - Dec 1 2016

Keywords

B cell malignancy
Chimeric antigen receptor
Immunotherapy

ASJC Scopus subject areas

Oncology
Radiology Nuclear Medicine and imaging
Cancer Research

MD Anderson CCSG core facilities

Flow Cytometry and Cellular Imaging Facility
Research Animal Support Facility
Small Animal Imaging Facility

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10.1007/s11307-016-0971-8

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Najjar, A. M., Manuri, P. R., Olivares, S., Flores, L., Mi, T., Huls, H., Shpall, E. J., Champlin, R. E., Turkman, N., Paolillo, V., Roszik, J., Rabinovich, B., Lee, D. A., Alauddin, M., Gelovani, J., & Cooper, L. J. N. (2016). Imaging of Sleeping Beauty-Modified CD19-Specific T Cells Expressing HSV1-Thymidine Kinase by Positron Emission Tomography. Molecular Imaging and Biology, 18(6), 838-848. https://doi.org/10.1007/s11307-016-0971-8

Najjar, AM, Manuri, PR, Olivares, S, Flores, L, Mi, T, Huls, H, Shpall, EJ , Champlin, RE, Turkman, N, Paolillo, V, Roszik, J, Rabinovich, B, Lee, DA, Alauddin, M, Gelovani, J & Cooper, LJN 2016, 'Imaging of Sleeping Beauty-Modified CD19-Specific T Cells Expressing HSV1-Thymidine Kinase by Positron Emission Tomography', Molecular Imaging and Biology, vol. 18, no. 6, pp. 838-848. https://doi.org/10.1007/s11307-016-0971-8

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

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doi = "10.1007/s11307-016-0971-8",

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AU - Najjar, Amer M.

AU - Manuri, Pallavi R.

AU - Olivares, Simon

AU - Flores, Leo

AU - Mi, Tiejuan

AU - Huls, Helen

AU - Shpall, Elizabeth J.

AU - Champlin, Richard E.

AU - Turkman, Nashaat

AU - Paolillo, Vincenzo

AU - Roszik, Jason

AU - Rabinovich, Brian

AU - Lee, Dean A.

AU - Alauddin, Mian

AU - Gelovani, Juri

AU - Cooper, Laurence J.N.

PY - 2016/12/1

Y1 - 2016/12/1

N2 - 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.

AB - 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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KW - Chimeric antigen receptor

KW - Immunotherapy

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

Abstract

Keywords

ASJC Scopus subject areas

MD Anderson CCSG core facilities

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