The role of viral dynamics and infectivity in models of oncolytic virotherapy for tumours with different motility

Abstract

The use of ad-hoc engineered viruses in the fight against tumours is one of the greatest ideas in cancer therapeutics within the last three decades. Together with other strategies such as immunotherapies, nanoparticles and adjunct therapies, the use of viral vectors in clinical trials and in the clinics has been and is still widely studied and pursued. The ability of those vectors to infiltrate and infect tumours represents one of the key attributes that regulates the success of such a strategy. Although some remarkable successes have been obtained, it is still not entirely clear how to achieve reliable protocols that can be routinely employed with confidence on a significant range of tumours. In this work, we thus concentrate on the study of different mathematical descriptions of virotherapy with the aim of better understanding the role of viral infectivity and viral dynamics in positive therapeutic outcomes. In particular, we compare probabilistic, individual approaches with continuous, spatially inhomogeneous models and investigate the importance of different tumour motility and different mathematical representations of viral infectivity. These formulations also allow us to arrive at better analytical characterisation of how waves of viral infections arise and propagate in tumours, providing interesting insights into therapy dynamics. Similarly to previous studies, oscillatory behaviours, stochasticity and cancers' diffusivities are all central to the eradication or the escape of tumours under virotherapy. Here, though, our results also show that the ability of viruses to infect tumours seems, in certain cases, more important to a final positive outcome than tumours' motility or even reproducibility. This could hopefully represent a first step into better insights into viral dynamics that may help clinicians to achieve consistently better outcomes.