Prime-boost using separate oncolytic viruses in combination with checkpoint blockade improves anti-tumour therapy

Area of Science:

• Immunology
• Virology
• Oncology

Background:

• Oncolytic virus therapy's anti-tumour effects rely on immune responses, influenced by virus type and delivery route.
• Intra-tumoral Reovirus induces CD8+ Th1 anti-tumour responses, while systemic VSV-ASMEL promotes CD4+ Th17 responses.

Purpose of the Study:

• To investigate the synergistic anti-tumour effects of combining Reovirus and VSV-ASMEL with anti-PD-1 immune checkpoint blockade.
• To enhance anti-tumour immunity by combining complementary CD8+ Th1 and CD4+ Th17 responses.

Main Methods:

• Mice with established subcutaneous B16 melanoma tumours were treated with intra-tumoral Reovirus, intravenous VSV-ASMEL, and/or anti-PD-1.
• Immune responses, including Th1 and Th17 profiles, were analyzed.
• Survival rates were assessed for different treatment combinations.

Main Results:

• Intra-tumoral Reovirus followed by intravenous VSV-ASMEL significantly improved survival.
• Combination with anti-PD-1 augmented both Th1 and Th17 responses.
• The triple combination of systemic Reovirus, VSV-ASMEL, and anti-PD-1 achieved long-term cures and enhanced survival.

Conclusions:

• Combining oncolytic viruses (Reovirus and VSV-ASMEL) with anti-PD-1 blockade creates a potent systemic anti-tumour immunovirotherapy.
• Complementary Th1 and Th17 immune responses are crucial for achieving enhanced and sustained anti-tumour activity.
• This multi-modal approach offers a promising strategy for effective cancer treatment.