Combined Oncolytic Virotherapy with Herpes Simplex Virus for Oral Squamous Cell Carcinoma

Abstract

Background: The effect of dual infection with herpes simplex virus type 1 (HSV-1) mutants on human oral squamous cell carcinoma (SCC) cells was examined. Materials and Methods: Human oral SCC cells were infected with γ₁34.5 gene-deficient HSV-1 R849 and HSV-1 HF that has multiple mutations and induces cell fusion. Cell viability was measured by LDH release assay. Athymic mice were injected with oral SCC cells into the buccal region to induce subcutaneous tumors. Results: Oral SCC cells were infected with R849, followed by infection with R849 or HF. Virus production was elevated by both strains of HSV-1. Although the release of LDH from R849-infected cells was increased by secondary infection with R849 or HF, the effect of HF was more remarkable. When nude mouse tumors were treated with R849, HF, R849+R849, or R849+HF, treatment with R849+HF was the most effective. Conclusion: These results suggest that fusion-inducing virus HF enhances the oncolytic ability of γ₁34.5 gene-deficient HSV-1 and provides a rationale for using fusogenic viruses as enhancing agents