J. W. Ady1, C. Johnsen1, K. Mojica1, J. Heffner1, D. Love1, A. Pugalenthi1, J. Belin1, J. R. Aguilar5, N. Chen5, Y. A. Yu5, A. Szalay5, Y. Fong4 1Memorial Sloan-Kettering Cancer Center,Surgery,New York, NY, USA 2University Of California – San Diego,3Department Of Radiation Medicine And Applied Sciences, Rebecca & John Moores Comprehensive Cancer Center,San Diego, CA, USA 3University Of Würzburg,4Department Of Biochemistry, Rudolph Virchow Center For Experimental Biomedicine, And Institute For Molecular Infection Biology,Würzburg, BAVARIA, Germany 4City Of Hope National Medical Center,Surgery,Duarte, CA, USA 5Genelux,Research And Development,San Diego, CALIFORNIA, USA
Introduction: Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver with limited treatment options and poor prognosis. Therefore, there is a great need to develop novel therapies for HCC. Oncolytic viruses that specifically infect, replicate within, and kill cancer cells represent an emerging and promising platform for cancer therapy. In this study we assess at the ability of GLV-2b372, a novel nonattenuated vaccinia virus derived from the Lister 1.1.1 strain, to kill HCC.
Methods: The infectivity, viral replication and cytotoxicity of GLV-2b372 was assayed in 4 human HCC cell lines. Huh-7 flank xenografts were generated in athymic nude mice. Mice were treated with intratumoral injections of GLV-2b372. Biodistribution of viral presence in animals treated with GLV-2b372 was assessed.
Results: Infectivity increased in a time and concentration dependent manner in all cell lines. All cell lines supported efficient replication of virus. Flank xenografts treated with GLV-2b372 demonstrated complete erradication of tumor in 75% of animals with significant tumor reduction as compared to controls (p < 0.05). Biodistribution confirmed sustained intratumoral presence of virus at 2 weeks post infection, with rapid clearance of tumor from all other tissues.
Conclusion: Our results demonstrate that the novel oncolytic vaccinia virus GLV-2b372 selectively infects and replicates in HCC tissue. We demonstrate infectivity and killing of HCC both in vitro and in vivo. These findings indicate that GLV-2b372 is a potent oncolytic vector that could serve as a promising platform for oncolytic cancer immunotherapy.