Optimization of Tumor Virotherapy with Recombinant Measles Viruses
Abstract Recombinant viruses based on the vaccine strain of measles virus have potent and selective activity against a wide range of tumors. Successful tumor therapy with these viruses (virotherapy) depends on efﬁcient infection of tumor cells by the virus. Infected cells express viral proteins that allow them to fuse with neighboring cells to form syncytia. Infection halts tumor cell replication and the syncytia ultimately die. Moreover, infected cells may produce new virus particles that proceed to infect additional tumor cells. The outcome of virotherapy depends on the
dynamic interactions between the uninfected tumor cells, infected cells, and the virus population. We present a model of tumor and virus interactions based on the phenomenologically established interactions between the three populations. Other similar models proposed in the literature are also discussed. The model parameters are obtained by ﬁtting the model to experimental data. We discuss equilibrium states and explore by simulations the impact of various initial conditions and perturbations of the system in an attempt to achieve tumor eradication. We show that the total dose of virus administered and the rate at which the tumor grows play determining roles on the outcome. If tumor growth can be slowed, the minimal dose of virus needed for curative therapy can be reduced substantially. An interesting prediction of the model is that virotherapy is more effective on larger tumors when deceleration of growth occurs.