Oncolytic virus therapy benefits from control theory

Abstract

Oncolytic virus therapy aims to eradicate tumours using viruses which only infect and destroy targeted tumour cells. It is urgent to improve understanding and outcomes of this promising cancer treatment because oncolytic virus therapy could provide sensible solutions for many patients with cancer. Recently, mathematical modelling of oncolytic virus therapy was used to study different treatment protocols for treating breast cancer cells with genetically engineered adenoviruses. Indeed, it is currently challenging to elucidate the number, the schedule, and the dosage of viral injections to achieve tumour regression at a desired level and within a desired time frame. Here, we apply control theory to this model to advance the analysis of oncolytic virus therapy. The control analysis of the model suggests that at least three viral injections are required to control and reduce the tumour from any initial size to a therapeutic target. In addition, we present an impulsive control strategy with an integral action and a state feedback control which achieves tumour regression for different schedule of injections. When oncolytic virus therapy is evaluated in silico using this feedback control of the tumour, the controller automatically tunes the dose of viral injections to improve tumour regression and to provide some robustness to uncertainty in biological rates. Feedback control shows the potential to deliver efficient and personalized dose of viral injections to achieve tumour regression better than the ones obtained by former protocols. The control strategy has been evaluated in silico with parameters that represent five nude mice from a previous experimental work. Together, our findings suggest theoretical and practical benefits by applying control theory to oncolytic virus therapy.