Oncolytic HSV-1 expressing GM-CSF and IL-12 enhances anti-tumor efficacy in immunocompetent murine melanoma model

Oncolytic virus therapy is a promising strategy for Cancer treatment. Herpes simplex virus type 1 (HSV-1) has been successfully used in oncolytic virotherapy. In the present research, we applied an HSV-1 synthetic genomics platform to construct two oncolytic viruses, oHSV-1.1 and oHSV-1.2. oHSV-1.1 had the virulence gene ICP34.5 and ICP47 deleted for attenuation, and oHSV-1.2 was additionally armed with murine granulocyte macrophage-colony stimulating factor (GM-CSF) and interleukin-12 (IL-12). The oncolytic viruses were evaluated in vitro and in an immunocompetent murine melanoma model. The animal experiments confirmed that both oncolytic viruses displayed antitumor efficacy, including inhibiting tumor growth and prolonging overall survival. Compared with oHSV-1.1, oHSV-1.2 demonstrated superior tumor growth suppression and enhanced antitumor efficacies, as evidenced by increased tumor cell Apoptosis, cytotoxic T cells and macrophages infiltration, IFN-γ production, and upregulation of inflammatory-related gene expression. Our research highlights the potential of oncolytic HSV-1 expressing both GM-CSF and IL-12 for melanoma therapy, and provides a promising strategy for further development of oncolytic virotherapy.

GM-CSF; Herpes simplex virus type I (HSV-1); IL-12; Melanoma; Oncolytic virus; Synthetic genomics.