Mathematical model of oncolytic virotherapy with Myxoma virus infection in cancer cells

Abstract

Oncolytic virotherapy is an innovative alternative to more conventional cancer therapies that is based on the ability of oncolytic viruses to specifically target and kill tumor cells. This therapy can activate the innate and adaptive immune response of the body achieving the destruction of cancer cells by the immune system. Myxoma virus is a poxvirus that infects in European rabbits, can also replicate in a variety of human cancer cells lines, which makes it an ideal candidate for oncolytic virotherapy. However, the dynamic mechanisms between the virus and the cancer cells are not completely understood. Mathematical models are useful tools to provide relevant insights about the dynamics that govern the interplay between normal and cancer cells and their viral parasites. In this study murine melanoma cancer cells were infected with a Myxoma virus expressing GFP (vMyx GFP) at low multiplicity of infection and pictures were taken in a fluorescence microscope every 30 minutes to determine infected cells. To understand the process of infection, namely the susceptible to infected conversion rates and the spatial effects of cell culture, we developed a mathematical model parameterized with the experiments described above that spatially explicitly simulates the process of infection. The model is an stochastic spatially explicit SI formulation that considers cancer cells and viral particles. With the model we were able to quantify and better understand this complex network of interactions. We were able to estimate important parameters concerning infection, proliferation and spatial dependency. We hope that the model will contribute to accelerate the development of a functional and effective oncolytic virotherapy with Myxoma virus.Support or Funding InformationOffice of the vice‐presidency of research at los Andes University