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Growth, Purification, and Titration of Oncolytic Herpes Simplex Virus
Published on: May 13, 2021
Oncolytic virotherapy for tumours following a Gompertz growth law
Adrianne L Jenner1, Peter S Kim1, Federico Frascoli2
1School of Mathematics and Statistics, University of Sydney, Sydney, NSW, Australia.
Abstract:
Oncolytic viruses are genetically engineered to treat growing tumours and represent a very promising therapeutic strategy. Using a Gompertz growth law, we discuss a model that captures the in vivo dynamics of a cancer under treatment with an oncolytic virus. With the aid of local stability analysis and bifurcation plots, the typical interactions between virus and tumour are investigated. The system shows a singular equilibrium and a number of nonlinear behaviours that have interesting biological consequences, such as long-period oscillations and bistable states where two different outcomes can occur depending on the initial conditions. Complete tumour eradication appears to be possible only for parameter combinations where viral characteristics match well with the tumour growth rate. Interestingly, the model shows that therapies with a high initial injection or involving a highly effective virus do not universally result in successful strategies for eradication. Further, the use of additional, "boosting" injection schedules does not always lead to complete eradication. Our framework, instead, suggests that low viral loads can be in some cases more effective than high loads, and that a less resilient virus can help avoid high amplitude oscillations between tumours and virus. Finally, the model points to a number of interesting findings regarding the role of oscillations and bistable states between a tumour and an oncolytic virus. Strategies for the elimination of such fluctuations depend strongly on the initial viral load and the combination of parameters describing the features of the tumour and virus.
Insights
Oncolytic virus therapy for cancer shows complex dynamics. Mathematical modeling reveals that complete tumor eradication is possible but depends on matching viral traits to tumor growth, not just high viral loads.
Area of Science:
- Oncology
- Mathematical Biology
- Virology
Background:
- Oncolytic viruses are engineered to target and destroy cancer cells, offering a promising therapeutic avenue.
- Understanding the complex interactions between oncolytic viruses and tumors in vivo is crucial for optimizing treatment strategies.
Purpose of the Study:
- To develop and analyze a mathematical model simulating cancer dynamics under oncolytic virus treatment.
- To investigate the influence of viral characteristics and administration schedules on treatment outcomes.
Main Methods:
- Utilized a Gompertz growth law to model tumor progression.
- Employed local stability analysis and bifurcation plots to explore virus-tumor interactions.
- Analyzed system dynamics, including oscillations and bistable states.
Main Results:
- Identified conditions for complete tumor eradication, emphasizing the importance of matching viral properties to tumor growth rates.
- Demonstrated that high initial viral doses or highly effective viruses do not guarantee eradication.
- Revealed that lower viral loads and less resilient viruses can be more effective in certain scenarios, avoiding detrimental oscillations.
Conclusions:
- Oncolytic virus therapy efficacy is highly dependent on specific parameter combinations, not solely on viral load or potency.
- Oscillations and bistable states significantly impact treatment outcomes, with strategies for their control linked to initial viral load and parameter tuning.
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