The Optimal Balance between Oncolytic Viruses and Natural Killer Cells: A Mathematical Approach

Oncolytic virotherapy (OV) is a cancer therapy utilizing lytic viruses that specifically target cancer cells for elimination. In this relatively new therapy, two contradictory observations have been made. Some studies showed that immune responses including activated natural killer (NK) cells post oncolytic viral infection increased the cancer cell death, while others reported that such initial immune responses diminished the anti-tumor efficacy, which was caused by premature viral clearance. In this paper, we present a mathematical model to investigate the effect of NK cells on oncolytic virotherapy. Particularly, we focused on the minimum condition for NK cells to be activated in terms of parameters and how the activation of NK cells interacts and changes the dynamics among cancer, infected cancer cells and oncolytic virus. Analytic works for the existence and stability conditions of equilibrium points are provided. Numerical results are in good agreement with analytic solutions. Our numerical results show that equilibrium points can be created or destroyed by the activation of NK cells in a dynamical system and suggest that the balance between the bursting rate of the virus and the activation rate of NK cells is a crucial factor for successful OV therapy.