Justin W Ady1, Jacqueline Heffner1, Kelly Mojica1, Clark Johnsen1, Laurence J Belin1, Damon Love1, Chin-Tung Chen1, Amudhan Pugalenthi1, Elizabeth Klein1, Nanhai G Chen2, Yong A Yu2, Aladar A Szalay3, Yuman Fong4. 1. Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY. 2. Genelux Corporation, San Diego Science Center, San Diego, CA; Department of Radiation Medicine and Applied Sciences, Rebecca & John Moores Comprehensive Cancer Center, University of California, San Diego, CA. 3. Genelux Corporation, San Diego Science Center, San Diego, CA; Department of Radiation Medicine and Applied Sciences, Rebecca & John Moores Comprehensive Cancer Center, University of California, San Diego, CA; Department of Biochemistry, Rudolph Virchow Center for Experimental Biomedicine, and Institute for Molecular Infection Biology, University of Würzburg, Würzburg, Germany. 4. Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY. Electronic address: fongy@mskcc.org.
Abstract
BACKGROUND: Sorafenib is the standard systemic therapy for unresectable or recurrent hepatocellular carcinoma (HCC) but adds minimal increase in survival. Therefore, there is a great need to develop novel therapies for advanced or recurrent HCC. One emerging field of cancer treatment involves oncolytic viruses that specifically infect, replicate within, and kill cancer cells. In this study, we examined the ability of GLV-1h68, a recombinant vaccinia virus derived from the vaccine strain that was used to eradicate smallpox, to kill sorafenib-resistant (SR) HCC cell lines. METHODS: Four SR HCC cell lines were generated by repeated passage in the presence of sorafenib. Median inhibitory concentration was determined for all cell lines. The infectivity, viral replication, and cytotoxicity of GLV-1h68 were assayed for both parental and SR HCC cells. RESULTS: Infectivity increased in a time and concentration-dependent manner in all cell lines. All cell lines supported efficient replication of virus. No difference between the rates of cell death between the parental and SR cell lines was observed. CONCLUSION: Our results demonstrate that the oncolytic vaccinia virus GLV-1h68 kills both parental and SR HCC cell lines efficiently. This study indicates that patients who have failed treatment with sorafenib remain viable candidates for oncolytic therapy.
BACKGROUND:Sorafenib is the standard systemic therapy for unresectable or recurrent hepatocellular carcinoma (HCC) but adds minimal increase in survival. Therefore, there is a great need to develop novel therapies for advanced or recurrent HCC. One emerging field of cancer treatment involves oncolytic viruses that specifically infect, replicate within, and kill cancer cells. In this study, we examined the ability of GLV-1h68, a recombinant vaccinia virus derived from the vaccine strain that was used to eradicate smallpox, to kill sorafenib-resistant (SR) HCC cell lines. METHODS: Four SR HCC cell lines were generated by repeated passage in the presence of sorafenib. Median inhibitory concentration was determined for all cell lines. The infectivity, viral replication, and cytotoxicity of GLV-1h68 were assayed for both parental and SR HCC cells. RESULTS: Infectivity increased in a time and concentration-dependent manner in all cell lines. All cell lines supported efficient replication of virus. No difference between the rates of cell death between the parental and SR cell lines was observed. CONCLUSION: Our results demonstrate that the oncolytic vaccinia virus GLV-1h68 kills both parental and SR HCC cell lines efficiently. This study indicates that patients who have failed treatment with sorafenib remain viable candidates for oncolytic therapy.
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