A battle between cancer and a virus: modeling oncolytic virotherapy
Mathematical Biosciences Institute, The Ohio State University
(March 13, 2014 10:20 AM - 11:15 AM)
Oncolytic virotherapy is a tumor treatment which uses viruses to selectively target and destroy cancer cells. Clinical trials have demonstrated varying degrees of success for the therapy with limitations predominantly due to barriers to viral spread throughout the tumor and the immune response to the virus.
Fusogenic viruses, capable of causing cell-to-cell fusion upon infection of a tumor cell, have shown promise as oncolytic agents in experimental studies. The fusion causes the formation of multinucleated syncytia which enhances viral spread through the tumor and eventually leads to cell death. We formulate a partial differential equations model with a moving boundary to describe the treatment of a spherical tumor with a fusogenic oncolytic virus. In this talk, I will discuss the existence and uniqueness of local solutions to the nonlinear hyperbolic-parabolic system. In a special case, a reduction to an ordinary differential equations system allows for a global stability analysis which provides a prediction of success or failure of the treatment. Numerical simulations demonstrate exponential growth or decay of the tumor depending on viral burst size and rate of syncytia formation.
I will also briefly discuss work in progress on modeling the upregulation of the matricellular protein CCN1 in oncolytic virotherapy of glioma. Overexpression of CCN1 has been shown experimentally to induce an antiviral immune response including the proinflammatory activation of macrophages. Understanding the interactions between the tumor, virus and immune response is critical to improving the efficacy of virotherapy.