Fusogenic activity of vesicular stomatitis virus glycoprotein plasmid in tumors as an enhancer of IL-12 gene therapy.

We have characterized the fusogenic activity of a plasmid expression system encoding vesicular stomatitis virus G protein (VSVG) in vitro and in vivo. Over 70% of murine colon and renal carcinoma cells (MC38 and Renca, respectively) transfected with VSVG plasmid in vitro fused and formed polykaryons upon incubation with pH 5.5 media. Using a plasmid expression system encoding VSVG and bacterial green fluorescent protein (GFP) formulated in a polyvinyl pyrrolidone (PVP) delivery system, diffusion of GFP throughout the VSVG-induced syncytia was shown in vivo in MC38 and Renca tumors. Moreover, tumor-bearing mice showed tumor growth inhibition following in vivo transfection with VSVG plasmid at an optimal dose of 48 microg. We have previously shown that direct injection of interleukin -12 (IL -12) plasmid complexed with PVP into tumors induces a strong immune response. In the current study, we assessed the ability of VSVG to elicit an antitumor response by enhancing cytokine gene delivery within the tumor mass. Tumor-bearing mice treated intratumorally with both VSVG/PVP and IL-12/PVP (48 and 24 microg, respectively) showed increase in tumor rejection when compared to IL- 12 plasmid alone (75% vs. 50%, respectively). These data suggest that VSVG gene therapy can be used in combination with other therapeutic genes to induce an antitumor response in vivo by enhancing the expression of the gene of interest.