Modelling heterogeneity in viral-tumour dynamics: The effects of gene-attenuation on viral characteristics

Publication date: 7 October 2018 Source:Journal of Theoretical Biology, Volume 454 Author(s): Adrianne Jenner, Chae-Ok Yun, Arum Yoon, Peter S. Kim, Adelle C.F. Coster The use of viruses as a cancer treatment is becoming increasingly more robust; however, there is still a long way to go before a completely successful treatment is formulated. One major challenge in the field is to select which virus, out of a burgeoning number of oncolytic viruses and engineered derivatives, can maximise both treatment spread and anticancer cytotoxicity. To assist in solving this problem, an in-depth understanding of the virus-tumour interaction is crucial. In this article, we present a novel integro-differential system with distributed delays embodying the dynamics of an oncolytic adenovirus with a fixed population of tumour cells in vitro, allowing for heterogeneity to exist in the virus and cell populations. The parameters of the model are optimised in a hierarchical manner, the purpose of which is not to obtain a perfect representation of the data. Instead, we place our parameter values in the correct region of the parameter space. Due to the sparse nature of the data it is not possible to obtain the parameter values with any certainty, but rather we demonstrate the suitability of the model. Using our model we quantify how modifications to the viral genome alter the viral characteristics, specifically how the attenuation of the E1B 19 and E1B 55 gene affect the system performance, a...
Source: Journal of Theoretical Biology - Category: Biology Source Type: research