Enhancing oncolytic virotherapy: Observations from a Voronoi Cell-Based model

Abstract

Oncolytic virotherapy is a promising cancer treatment using genetically modified viruses. Unfortunately, virus particles rapidly decay inside the body, significantly hindering their efficacy. In this article, treatment perturbations that could overcome obstacles to oncolytic virotherapy are investigated through the development of a Voronoi Cell-Based model (VCBM). The VCBM derived captures the interaction between an oncolytic virus and cancer cells in a 2-dimensional setting by using an agent-based model, where cell edges are designated by a Voronoi tessellation. Here, we investigate the sensitivity of treatment efficacy to the configuration of the treatment injections for different tumour shapes: circular, rectangular and irregular. The model predicts that multiple off-centre injections improve treatment efficacy irrespective of tumour shape. Additionally, we investigate delaying the infection of cancer cells by modifying viral particles with a substance such as alginate (a hydrogel polymer used in a range of cancer treatments). Simulations of the VCBM show that delaying the infection of cancer cells, and thus allowing more time for virus dissemination, can improve the efficacy of oncolytic virotherapy. The simulated treatment noticeably decreases the tumour size with no increase in toxicity. Improving oncolytic virotherapy in this way allows for a more effective treatment without changing its fundamental essence.

Keywords: Agent-based model; Cell-based model; Cellular automaton; Mathematical modelling; Oncolytic virus; Tumour; Voronoi tessellation.