The role of viral infectivity in oncolytic virotherapy outcomes: A mathematical study

TL;DR

This mathematical study models virus-tumour interactions in oncolytic virotherapy, revealing that increasing viral infectivity alone cannot fully eradicate tumours and may cause oscillations and surges, indicating the need for combined treatment strategies.

Contribution

The paper introduces a mathematical model incorporating infectivity parameters and analyzes their impact on therapy outcomes, highlighting limitations of viral infectivity enhancement alone.

Findings

Enhancing infectivity does not guarantee tumour eradication.

Oscillations in tumour size occur, preventing full destruction.

Bifurcation analysis shows potential for surges in tumour load.

Abstract

A model capturing the dynamics between virus and tumour cells in the context of oncolytic virotherapy is presented and analysed. The ability of the virus to be internalised by uninfected cells is described by an infectivity parameter, which is inferred from available experimental data. The parameter is also able to describe the effects of changes in the tumour environment that affect viral uptake from tumour cells. Results show that when a virus is inoculated inside a growing tumour, strategies for enhancing infectivity do not lead to a complete eradication of the tumour. Within typical times of experiments and treatments, we observe the onset of oscillations, which always prevent a full destruction of the tumour mass. These findings are in good agreement with available laboratory results. Further analysis shows why a fully successful therapy cannot exist for the proposed model and that care must be taken when designing and engineering viral vectors with enhanced features. In particular, bifurcation analysis reveals that creating longer lasting virus particles or using strategies for reducing infected cell lifespan can cause unexpected and unwanted surges in the overall tumour load over time. Our findings suggest that virotherapy alone seems unlikely to be effective in clinical settings unless adjuvant strategies are included.