TY - JOUR
T1 - Suicide genes
T2 - Monitoring cells in patients with a safety switch
AU - Eissenberg, Linda G.
AU - Rettig, Michael
AU - Dehdashti, Farrokh
AU - Piwnica-Worms, David
AU - DiPersio, John F.
N1 - Publisher Copyright:
© 2014 Eissenberg, Rettig, Dehdashti, Piwnica-Worms and DiPersio.
PY - 2014
Y1 - 2014
N2 - 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 18F-9-(4-fluoro-3-hydroxymethylbutyl)guanine (18FHBG) 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.
AB - 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 18F-9-(4-fluoro-3-hydroxymethylbutyl)guanine (18FHBG) 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.
KW - PET-imaging
KW - gene therapy
KW - regenerative medicine
KW - suicide gene
KW - thymidine kinase
KW - transplant biology
UR - http://www.scopus.com/inward/record.url?scp=84949115261&partnerID=8YFLogxK
U2 - 10.3389/fphar.2014.00241
DO - 10.3389/fphar.2014.00241
M3 - Article
C2 - 25414668
AN - SCOPUS:84949115261
SN - 1663-9812
VL - 5
JO - Frontiers in Pharmacology
JF - Frontiers in Pharmacology
IS - NOV
M1 - 241
ER -