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

Journal: Surgery 2014;156(2):263-9

PMID: 24957667

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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.

Address: Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY.; 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.; 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.; Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY. Electronic address: [email protected].

DOI: 10.1016/j.surg.2014.03.031