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Suicide genes: monitoring cells in patients with a safety switch

Eissenberg LG1, Rettig M1, Dehdashti F2, Piwnica-Worms D3, DiPersio JF1.

Front Pharmacol. 2014;5:241.

1Department of Internal Medicine, Washington University School of Medicine, St. Louis MO, USA.and

2Department of Radiology, Washington University School of Medicine, St. Louis MO, USA.and

3Department of Radiology, Washington University School of Medicine, St. Louis MO, USA ; Department of Cancer Systems Imaging, University of Texas MD Anderson Cancer Center Houston, TX, USA.

 

Abstract

Clinical trials increasingly incorporate suicide genes either as direct lytic agents for tumors or as safety switches in therapies based on genetically modified cells. Suicide genes can also be used as non-invasive reporters to monitor the biological consequences of administering genetically modified cells to patients and gather information relevant to patient safety. These genes can monitor therapeutic outcomes addressable by early clinical intervention. As an example, our recent clinical trial used (18)F-9-(4-fluoro-3-hydroxymethylbutyl)guanine ((18)FHBG) and positron emission tomography (PET)/CT scans to follow T cells transduced with herpes simplex virus thymidine kinase after administration to patients. Guided by preclinical data we ultimately hope to discern whether a particular pattern of transduced T cell migration within patients reflects early development of graft vs. host disease. Current difficulties in terms of choice of suicide gene, biodistribution of radiolabeled tracers in humans vs. animal models, and threshold levels of genetically modified cells needed for detection by PET/CT are discussed. As alternative suicide genes are developed, additional radiolabel probes suitable for imaging in patients should be considered.

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