The oncolytic virus VT09X optimizes immune checkpoint therapy in low immunogenic melanoma

Area of Science:

• Oncolytic virotherapy
• Cancer immunology
• Immunotherapy

Background:

• Tumors with low immune cell infiltration poorly respond to immune checkpoint therapies.
• Oncolytic viruses can modulate the tumor microenvironment and enhance anti-tumor immunity.
• Combination strategies are needed to overcome resistance to current immunotherapies.

Purpose of the Study:

• To investigate the efficacy of an engineered HSV-1 oncolytic virus combined with a PD-1 antibody (pembrolizumab) in a preclinical melanoma model.
• To evaluate the impact of this combination on tumor immune infiltration and survival.
• To assess systemic immune changes induced by the combination therapy.

Main Methods:

• Engineering of an HSV-1 based oncolytic virus.
• Treatment of hPD-1 knock-in mice bearing B16-F10 melanoma with the oncolytic virus and pembrolizumab.
• Analysis of tumor immune cell infiltration (CD8+, CD4+ T cells), IFN-γ secretion, PD-L1 expression.
• Monitoring of overall survival and peripheral blood lymphocyte proportions.

Main Results:

• The combination therapy significantly enhanced CD8+ and CD4+ T cell infiltration into tumors.
• Increased IFN-γ secretion and PD-L1 expression were observed in the tumor microenvironment.
• Combination treatment led to prolonged overall survival in treated mice.
• Systemic alterations in lymphocyte populations were detected in peripheral blood.

Conclusions:

• Engineered oncolytic viruses can serve as a potent platform for combination immunotherapy.
• This approach can overcome resistance to immune checkpoint therapy by enhancing anti-tumor immunity.
• The combination of oncolytic viruses and PD-1 blockade shows significant therapeutic potential for non-immunogenic tumors.