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.
T cell Immunotherapy PET Human nuclear reporter gene Reporter probe Chimeric antigen receptors Nucleoside kinases
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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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