Modeling Oncolytic Vaccinia Virus Therapy Highlights Neutrophil Impact on Tumor Suppression∗

A bstract Oncolytic vaccinia viruses (OVVs) present a promising approach for melanoma treatment due to their ability to selectively infect and lyse tumor cells. In this study, we use an ordinary differential equation (ODE) model of tumor growth inhibited by OVV activity to parameterize previous research on the effect of neutrophil depletion in B16-F10 melanoma tumors in mice. We find that the data are best fit by a model that accounts for neutrophil-mediated viral clearance, and that neutrophil depletion provides a mechanism for enhanced OVV efficacy and tumor reduction. We also find that parameter estimates for the most effective OVV regime share characteristics, most notably a low viral clearance rate by neutrophils, that might explain the improved outcomes. Further studies examining the impact of neutrophil modulation across different tumor models may help elucidate the extent to which these findings generalize and inform the design of novel OVV-based cancer therapies.