Agent-based and continuum models for spatial dynamics of infection by oncolytic viruses

TL;DR

This study develops and compares agent-based and continuum models to understand the spatial spread of oncolytic viruses in tumors, revealing how movement types and spatial constraints influence infection dynamics and therapy outcomes.

Contribution

It introduces a stochastic agent-based model for tumor infection by oncolytic viruses and systematically compares it with continuum models, highlighting the impact of movement and spatial constraints.

Findings

Undirected movement models agree well with analytical results.

Pressure-driven movement shows confined infection and irregular growth patterns.

Spatial constraints significantly affect virotherapy effectiveness.

Abstract

The use of oncolytic viruses as cancer treatment has received considerable attention in recent years, however the spatial dynamics of this viral infection is still poorly understood. We present here a stochastic agent-based model describing infected and uninfected cells for solid tumours, which interact with viruses in the absence of an immune response. Two kinds of movement, namely undirected random and pressure-driven movements, are considered: the continuum limit of the models is derived and a systematic comparison between the systems of partial differential equations and the individual-based model, in one and two dimensions, is carried out. In the case of undirected movement, a good agreement between agent-based simulations and the numerical and well-known analytical results for the continuum model is possible. For pressure-driven motion, instead, we observe a wide parameter range in which the infection of the agents remains confined to the center of the tumour, even though the continuum model shows traveling waves of infection; outcomes appear to be more sensitive to stochasticity and uninfected regions appear harder to invade, giving rise to irregular, unpredictable growth patterns. Our results show that the presence of spatial constraints in tumours' microenvironments limiting free expansion has a very significant impact on virotherapy. Outcomes for these tumours suggest a notable increase in variability. All these aspects can have important effects when designing individually tailored therapies where virotherapy is included.