Abstract
Adoptive cell transfer immunotherapy has demonstrated significant promise in the treatment of cancer, with long-term, durable responses. T cells expressing T cell receptors (TCRs) that recognize tumor antigens, or engineered with chimeric antigen receptors (CARs) can recognize and eliminate tumor cells even in advanced disease. Positron emission tomography (PET) imaging with nuclear reporter genes, a noninvasive method to track and monitor function of engineered cells in vivo, allows quantitative, longitudinal monitoring of these cells, including their expansion/contraction, migration, retention at target and off-target sites, and biological state. As an additional advantage, some reporter genes also exhibit “suicide potential” permitting the safe elimination of adoptively transferred T cells in instances of adverse reaction to therapy. Here, we describe the production of human nuclear reporter gene-expressing T cells and noninvasive PET imaging to monitor their cell fate in vivo.
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References
Rosenberg SA, Restifo NP (2015) Adoptive cell transfer as personalized immunotherapy for human cancer. Science 348(6230):62–68
Couzin-Frankel J (2013) Breakthrough of the year 2013. Cancer immunotherapy. Science 342(6165):1432–1433
Fesnak AD, June CH, Levine BL (2016) Engineered T cells: the promise and challenges of cancer immunotherapy. Nat Rev Cancer 16(9):566–581
Sadelain M, Brentjens R, Riviere I (2013) The basic principles of chimeric antigen receptor design. Cancer Discov 3(4):388–398
Cartellieri M et al (2010) Chimeric antigen receptor-engineered T cells for immunotherapy of cancer. J Biomed Biotechnol 2010:956304
Sadelain M (2015) CAR therapy: the CD19 paradigm. J Clin Invest 125(9):3392–3400
Morello A, Sadelain M, Adusumilli PS (2016) Mesothelin-targeted CARs: driving T cells to solid tumors. Cancer Discov 6(2):133–146
Restifo NP, Smyth MJ, Snyder A (2016) Acquired resistance to immunotherapy and future challenges. Nat Rev Cancer 16(2):121–126
Moynihan KD et al (2006) Eradication of large established tumors in mice by combination immunotherapy that engages innate and adaptive immune responses. Nat Med 22(12):1402–1410
Lucignani G et al (2006) Molecular imaging of cell-mediated cancer immunotherapy. Trends Biotechnol 24(9):410–418
Akins EJ, Dubey P (2008) Noninvasive imaging of cell-mediated therapy for treatment of cancer. J Nucl Med 49(Suppl 2):180S–195S
Yaghoubi SS et al (2012) Positron emission tomography reporter genes and reporter probes: gene and cell therapy applications. Theranostics 2(4):374–391
Sadelain M (2009) T-cell engineering for cancer immunotherapy. Cancer J 15(6):451–455
Wang X, Riviere I (2016) Clinical manufacturing of CAR T cells: foundation of a promising therapy. Mol Ther Oncolytics 3:16015
Likar Y et al (2010) A new pyrimidine-specific reporter gene: a mutated human deoxycytidine kinase suitable for PET during treatment with acycloguanosine-based cytotoxic drugs. J Nucl Med 51(9):1395–1403
Yaghoubi SS et al (2009) Noninvasive detection of therapeutic cytolytic T cells with 18F-FHBG PET in a patient with glioma. Nat Clin Pract Oncol 6(1):53–58
Ponomarev V et al (2001) Imaging TCR-dependent NFAT-mediated T-cell activation with positron emission tomography in vivo. Neoplasia 3(6):480–488
Minn I et al (2014) Molecular-genetic imaging of cancer. Adv Cancer Res 124:131–169
Shu CJ et al (2009) Quantitative PET reporter gene imaging of CD8+ T cells specific for a melanoma-expressed self-antigen. Int Immunol 21(2):155–165
McCracken MN et al (2015) Noninvasive detection of tumor-infiltrating T cells by PET reporter imaging. J Clin Invest 125(5):1815–1826
Dobrenkov K et al (2008) Monitoring the efficacy of adoptively transferred prostate cancer-targeted human T lymphocytes with PET and bioluminescence imaging. J Nucl Med 49(7):1162–1170
Dubey P et al (2003) Quantitative imaging of the T cell antitumor response by positron-emission tomography. Proc Natl Acad Sci U S A 100(3):1232–1237
Hoekstra ME et al (2015) Assessing T lymphocyte function and differentiation by genetically encoded reporter systems. Trends Immunol 36(7):392–400
Moroz MA et al (2015) Comparative analysis of T cell imaging with human nuclear reporter genes. J Nucl Med 56(7):1055–1060
Sadelain M, Frassoni F, Riviere I (2000) Issues in the manufacture and transplantation of genetically modified hematopoietic stem cells. Curr Opin Hematol 7(6):364–377
Zanzonico P et al (2006) [131I]FIAU labeling of genetically transduced, tumor-reactive lymphocytes: cell-level dosimetry and dose-dependent toxicity. Eur J Nucl Med Mol Imaging 33(9):988–997
Thie JA (2004) Understanding the standardized uptake value, its methods, and implications for usage. J Nucl Med 45(9):1431–1434
Loening AM, Gambhir SS (2003) AMIDE: a free software tool for multimodality medical image analysis. Mol Imaging 2(3):131–137
Schneider CA, Rasband WS, Eliceiri KW (2012) NIH image to ImageJ: 25 years of image analysis. Nat Methods 9(7):671–675
Rosset A, Spadola L, Ratib O (2004) OsiriX: an open-source software for navigating in multidimensional DICOM images. J Digit Imaging 17(3):205–216
Acknowledgments
This work was supported by the NIH P50 CA86438, R01 CA163980, and R01 CA161138 grants, Mr. William H. Goodwin and Mrs. Alice Goodwin and the Commonwealth Foundation for Cancer Research and The Experimental Therapeutics Center of Memorial Sloan-Kettering Cancer Center, NIH Small-Animal Imaging Research Program (SAIRP), NIH Shared Instrumentation Grant No. 1 S10 RR020892-01, NIH Shared Instrumentation Grant No. 1 S10 RR028889-01, and NIH Center Grant P30 CA08748.
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Lee, J.T., Moroz, M.A., Ponomarev, V. (2018). Imaging T Cell Dynamics and Function Using PET and Human Nuclear Reporter Genes. In: Dubey, P. (eds) Reporter Gene Imaging. Methods in Molecular Biology, vol 1790. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-7860-1_13
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DOI: https://doi.org/10.1007/978-1-4939-7860-1_13
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