Background
Peritoneal carcinomatosis (PC) is a terminal progression of colorectal cancer (CRC).
Poor response to cytoreductive operation and chemotherapy coupled with the inability
to reliably track disease progression by the use of established diagnostic methods,
make this a deadly disease. We examined the effectiveness of the oncolytic vaccinia
virus GLV-1h153 as a therapeutic and diagnostic vehicle. We believe that viral expression
of the human sodium iodide transporter (hNIS) provides both real-time monitoring of
viral therapy and effective treatment of colorectal peritoneal carcinomatosis (CRPC).
Methods
Infectivity and cytotoxic effect of GLV-1h153 on CRC cell lines was assayed in vitro.
Viral replication was examined by standard viral plaque assays. Orthotopic CRPC xenografts
were generated in athymic nude mice and subsequently administered GLV-1h153 intraperitoneally.
A decrease in tumor burden was assessed by mass. Orthotopic tumors were visualized
by single-photon emission computed tomography/computed tomography after Iodine (131I) administration and by fluorescence optical imaging.
Results
GLV-1h153 infected and killed CRC cells in a time- and concentration-dependent manner.
Viral replication demonstrated greater than a 2.35 log increase in titer over 4 days.
Intraperitoneal treatment of orthotopic CRPC xenografts resulted in a substantial
decrease in tumor burden. Infection of orthotopic xenografts was therapeutic and facilitated
monitoring by 131I–single-photon emission computed tomography/computed tomography via expression of
hNIS in infected tissue.
Conclusion
GLV-1h153 kills CRC in vitro effectively and decreases tumor burden in vivo. We demonstrate
that GLV-1h153 can be used as an agent to provide accurate delineation of tumor burden
in vivo. These findings indicate that GLV-1h153 has potential for use as a therapeutic
and diagnostic agent in the treatment of CRPC.
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Article info
Publication history
Accepted:
September 8,
2014
Footnotes
Supported in part by grant for translational research from French National Cancer Institute (INCa) (C.E.), training grant T 32 CA09501 (J.C.), grants RO1 CA 76416 and RO1 CA/DK80982 (Y.F.) from the National Institutes of Health, grant BC024118 from the U.S. Army (Y.F.), grant IMG0402501 from the Susan G. Komen Foundation (Y.F.), and grant 032047 from the Flight Attendant Medical Research Institute (Y.F.). Y.F. is a scientific consultant to Genentech and Genelux; N.C., T.Y., and A.A.S. are employees of Genelux Corporation.
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© 2015 Elsevier Inc. Published by Elsevier Inc. All rights reserved.
