Oncolytic reovirus enhances the effect of CEA immunotherapy when combined with PD1-PDL1 inhibitor in a colorectal cancer model

May 12, 2025Immunotherapy

Reovirus boosts CEA immunotherapy combined with PD1-PDL1 blocker in colorectal cancer

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Abstract

The combination therapy led to the lowest tumor growth and the highest level of cytotoxic immunity in a mouse model.

The triple therapy included an oncolytic reovirus, an adenovector expressing carcinoembryonic antigen, and a PD-1/PD-L1 inhibitor.
Foxp3 levels in the tumor microenvironment decreased, indicating reduced immunosuppressive effects.
Secretion of Tumor necrosis factor-α (TNF-α) was lower in the combination therapy group compared to control groups.
The combination therapy resulted in fewer mitotic figures and a greater number of tumor-infiltrating lymphocytes.

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AIM: The effectiveness of immunotherapy with tumor associated antigen vaccines can be enhanced by combining oncolytic viruses with immune checkpoint inhibitors. This study evaluates the efficacy of oncolytic reovirus in combination with an adenovector expressing carcinoembryonic antigen (Ad-CEA) and a programmed death-1/programmed death-ligand 1 (PD-1/PD-L1) inhibitor in a mouse model.

METHODS: Mice bearing CEA-expressing CT26 tumor cells were immunized with Ad-CEA along with a PD-1/PD-L1 inhibitor. Subsequently, three doses of reovirus were injected into the tumors. Tumor size, histopathological examination, CD8 and FOXP3 expression, the cytotoxicity of spleen T cell lymphocytes, and the secretion of Interferon-γ (IFN-γ) and Tumor necrosis factor- α (TNF-α) were examined.

RESULTS: The triple therapy used in this study resulted in the lowest tumor growth and the highest level of cytotoxic immunity. The Foxp3 levels in the tumor microenvironment and TNF-α secretion decreased compared to other control groups. Additionally, this group exhibited the lowest number of mitotic figures and the highest amount of tumor-infiltrating lymphocytes.

CONCLUSION: The combination of tumor vaccines with oncolytic viruses significantly improves treatment efficacy. Furthermore, inhibiting the PD-1/PD-L1 interaction during vaccination and also with virotherapy enhances immunovirotherapy by reducing immunosuppressive effects and stimulating the immune system, leading to improved therapeutic outcomes.

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Oncolytic reovirus enhances the effect of CEA immunotherapy when combined with PD1-PDL1 inhibitor in a colorectal cancer model

Abstract

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