Oncolytic immunotherapy using recombinant vaccinia virus GLV-1h68 kills sorafenib-resistant hepatocellular carcinoma efficiently

Justin W. Ady, Jacqueline Heffner, Kelly Mojica, Clark Johnsen, Laurence J. Belin, Damon Love, Chin Tung Chen, Amudhan Pugalenthi, Elizabeth Klein, Nanhai G. Chen, Yong A. Yu, Aladar A. Szalay, Yuman Fong

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)263-269
Number of pages7
JournalSurgery (United States)
Volume156
Issue number2
DOIs
StatePublished - Aug 2014

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