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Adrianne2018 - Modelling combined virotherapy and immunotherapy: strengthening the antitumour immune response mediated by IL-12 and GM-CSF expression

ABSTRACT: Modelling combined virotherapy and immunotherapy:strengthening the antitumour immune response mediated byIL-12 and GM-CSF expression Adrianne L. Jennera, Chae-Ok Yunb, Arum Yoonb, Adelle C. F. Costercand Peter S. Kimaa School of Mathematics and Statistics, University of Sydney, Sydney, Australia;bDepartment ofBioengineering, Hanyang University, Seoul, Korea;cSchool of Mathematics and Statistics, University of NewSouth Wales, Sydney, Australia ABSTRACT Combined virotherapy and immunotherapy has been emergingas a promising and effective cancer treatment for some time.Intratumoural injections of an oncolytic virus instigate an immunereaction in the host, resulting in an influx of immune cells tothe tumour site. Through combining an oncolytic viral vector withimmunostimulatory cytokines an additional antitumour immuneresponse can be initiated, whereby immune cells induce apoptosisin both uninfected and virus infected tumour cells. We developa mathematical model to reproduce the experimental results fortumour growth under treatment with an oncolytic adenovirus co-expressing the immunostimulatory cytokines interleukin 12 (IL-12)and granulocyte-monocyte colony stimulating factor (GM-CSF). Byexploring heterogeneity in the immune cell stimulation by thetreatment, we find a subset of the parameter space for the immunecell induced apoptosis rate, in which the treatment will be lesseffective in a short time period. Therefore, we believe the bivariatenature of treatment outcome, whereby tumours are either completelyeradicated or grow unbounded, can be explained by heterogeneity inthis immune characteristic. Furthermore, the model highlights theapparent presence of negative feedback in the helper T cell and APCstimulation dynamics, when IL-12 and GM-CSF are co-expressed asopposed to individually expressed by the viral vector.

SUBMITTER: Mohammad Umer Sharif Shohan

PROVIDER: MODEL1912120003 | BioModels | 2020-01-09

REPOSITORIES: BioModels

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Project description:The paper describes a model of oncolytic virotherapy. Created by COPASI 4.26 (Build 213) This model is described in the article: Mathematical Modelling of the Interaction Between Cancer Cells and an Oncolytic Virus: Insights into the Effects of Treatment Protocols Adrianne L. Jenner, Chae-Ok Yun, Peter S. Kim, Adelle C. F. Coster Bull Math Biol (2018) 80:1615–1629 Abstract: Oncolyticvirotherapyisanexperimentalcancertreatmentthatusesgenet- ically engineered viruses to target and kill cancer cells. One major limitation of this treatment is that virus particles are rapidly cleared by the immune system, preventing them from arriving at the tumour site. To improve virus survival and infectivity Kim et al. (Biomaterials 32(9):2314–2326, 2011) modified virus particles with the polymer polyethylene glycol (PEG) and the monoclonal antibody herceptin. Whilst PEG mod- ification appeared to improve plasma retention and initial infectivity, it also increased the virus particle arrival time. We derive a mathematical model that describes the inter- action between tumour cells and an oncolytic virus. We tune our model to represent the experimental data by Kim et al. (2011) and obtain optimised parameters. Our model provides a platform from which predictions may be made about the response of cancer growth to other treatment protocols beyond those in the experiments. Through model simulations, we find that the treatment protocol affects the outcome dramatically. We quantify the effects of dosage strategy as a function of tumour cell replication and tumour carrying capacity on the outcome of oncolytic virotherapy as a treatment. The relative significance of the modification of the virus and the crucial role it plays in optimising treatment efficacy are explored. To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models . To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

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Adrianne2018 - Modelling combined virotherapy and immunotherapy: strengthening the antitumour immune response mediated by IL-12 and GM-CSF expression

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