Mathematical modelling of oncolytic vaccinia virus therapy highlights neutrophil impact on tumour suppression.

Abstract

Oncolytic vaccinia viruses (OVVs) present a promising approach for melanoma treatment due to their ability to selectively infect and lyse tumour cells. However, OVV therapy has shown poor long-term outcomes. In this study, we use an ordinary differential equation model of tumour growth inhibited by OVV activity to characterize the effect of neutrophil depletion in B16-F10 melanoma tumours in mice. We find that the data can be fit by a model that accounts for neutrophil-mediated viral clearance. The model allows for two fixed points: a disease-free equilibrium, where the tumour is eradicated, and chronic infection, where the tumour is controlled but not eliminated. The model correctly predicts enhanced OVV effectiveness in the presence of chemotherapeutic neutrophil modulation, with OVV treatment in combination with neutrophil depletion driving the system from the chronic infection equilibrium to the disease-free equilibrium. We also find that parameter estimates for the most effective OVV regime share characteristics, most notably a low viral clearance rate, suggesting that improved outcomes are due to longer-lasting viral infections. Further studies examining the impact of neutrophil modulation across different tumour models can help elucidate the extent to which these findings generalize and inform the design of novel OVV-based cancer therapies.