SSAT - Anti-Angiogenic Gene Therapy With Recombinant Oncolytic Vaccinia Virus Glv-1h164 Efficiently Kills Hepatocellular Carcinoma

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Anti-Angiogenic Gene Therapy With Recombinant Oncolytic Vaccinia Virus Glv-1h164 Efficiently Kills Hepatocellular Carcinoma
Justin W. Ady^*¹, Kelly Mojica¹, Laurence J. Belin^1,2, Damon Love^1,2, Clark Johnsen¹, Richard J. Aguilar³, Nanhai G. Chen³, Amudhan Pugalenthi¹, Yong a. Yu³, Aladar a. Szalay³, Yuman Fong¹
¹Surgery, Memorial Sloan Kettering Cancer Center, New York, NY; ²Surgery, Weill Cornell Medical College, New York, NY; ³Genelux, San Diego, CA

Introduction: Angiogenesis is crucial to tumor growth and metastasis of hepatocellular carcinoma (HCC). With no curative therapies available for patients with advanced stage disease, the exploitation of anti-angiogenic proteins is promising for the development of novel treatment options. As a therapy, oncolytic viruses selectively infect, replicate within, and kill cancer cells. During the replication life cycle, oncolytic viruses can also produce therapeutic proteins. In this study, we look at the ability of the oncolytic vaccinia virus GLV-1h164 to kill HCC and to deliver the anti-angiogenic protein GLAF-2 to tumor tissue.
Methods: Infectivity and cytotoxicity of four HCC cell lines were assayed in vitro. Standard viral plaque assays were used to examine viral replication. Flank HCC xenografts were generated in athymic nude mice and treated with intratumoral GLV-1h164 to assess for tumor growth inhibition. Expression of GLAF-2 was confirmed in vitro and in vivo using fluorescent microscopy.

Results: GLV-1h164 infected and killed all cell lines in a time and concentration dependent manner with 80% to 100% cell death seen by day 5 in all cell lines (Figure 1). Efficient replication of GLV-1h164 occurred in all cell lines. Two weeks after intratumoral treatment of flank HCC xenografts with GLV-1h164, significant inhibition of tumor growth was demonstrated. Fluorescent microscopy confirmed presence of vaccinia virus and GLAF-2 both in vitro and in vivo (Figure 2).

Conclusions: We demonstrate that oncolytic vaccinia virus GLV-1h164 expresses the anti-angiogenic molecule GLAF-2 in vivo and efficiently kills HCC tumor cell lines. These results encourage future clinical trials of GLV-1h164 as a novel therapy option in the treatment of advanced HCC.

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