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

Area of Science:

• Oncology
• Virology
• Immunotherapy

Background:

• Oncolytic virus therapy utilizes engineered viruses to selectively target and destroy cancer cells.
• Herpes simplex virus type 1 (HSV-1) is a well-established platform for developing oncolytic viruses.
• Melanoma remains a significant challenge, necessitating novel therapeutic strategies.

Purpose of the Study:

• To construct and evaluate novel oncolytic HSV-1 vectors for melanoma therapy.
• To assess the antitumor efficacy of two engineered HSV-1 variants, oHSV-1.1 and oHSV-1.2, in vitro and in vivo.
• To compare the therapeutic potential of a standard attenuated HSV-1 (oHSV-1.1) with a cytokine-armed HSV-1 (oHSV-1.2).

Main Methods:

• Construction of two oncolytic HSV-1 viruses using a synthetic genomics platform.
• oHSV-1.1: deletion of virulence genes ICP34.5 and ICP47 for attenuation.
• oHSV-1.2: further arming with murine granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-12 (IL-12).
• In vitro and in vivo evaluation in an immunocompetent murine melanoma model.

Main Results:

• Both oHSV-1.1 and oHSV-1.2 demonstrated significant antitumor efficacy, inhibiting tumor growth and prolonging survival in the murine melanoma model.
• oHSV-1.2 exhibited superior tumor suppression compared to oHSV-1.1.
• Enhanced antitumor effects of oHSV-1.2 included increased tumor cell apoptosis, greater infiltration of cytotoxic T cells and macrophages, elevated IFN-γ production, and upregulation of inflammatory genes.

Conclusions:

• Oncolytic HSV-1 expressing both GM-CSF and IL-12 (oHSV-1.2) holds significant potential for melanoma therapy.
• The engineered oncolytic virus oHSV-1.2 represents a promising strategy for advancing oncolytic virotherapy development.
• Further preclinical and clinical investigations are warranted to translate these findings into effective melanoma treatments.