Mathematical Modeling of the Role of Cytokines in Sindbis Virus Treatment of Glioblastoma.

Oncolytic viruses, specifically Sindbis virus (SINV), combined with cytokines show promising results in slowing glioma progression, but a quantitative understanding of their effects remains limited. In this study, we use an ordinary differential equation (ODE) model to examine the effect of adding cytokines to oncolytic SINV therapy. We fit the mathematical model to data extracted from published tumor growth curves to estimate key model parameters. We find that there are statistically significant differences between the infection rates of SINV and cytokine-bearing SINV, as well as differences in the cytokine's ability to reduce viral production. Model simulations show that the addition of cytokines causes an almost immediate reduction in the tumor size caused by the increased viral infection rate. The simultaneous reduction in viral production caused by the cytokines results in oscillations in virus, cytokines, and tumor volume. By providing parameter estimates for key biological processes, our model can help optimize treatment strategies and guide future research in oncolytic virotherapy.