  Oncolytic virotherapy (OV) has been emerging as a promising novel cancer
treatment that may be further combined with the existing therapeutic modalities
to enhance their effects. To investigate how OV could enhance chemotherapy, we
propose an ODE based model describing the interactions between tumour cells,
the immune response, and a treatment combination with chemotherapy and
oncolytic viruses. Stability analysis of the model with constant chemotherapy
treatment rates shows that without any form of treatment, a tumour would grow
to its maximum size. It also demonstrates that chemotherapy alone is capable of
clearing tumour cells provided that the drug efficacy is greater than the
intrinsic tumour growth rate. Furthermore, OV alone may not be able to clear
tumour cells from body tissue but would rather enhance chemotherapy if viruses
with high viral potency are used. To assess the combined effect of OV and
chemotherapy we use the forward sensitivity index to perform a sensitivity
analysis, with respect to chemotherapy key parameters, of the virus basic
reproductive number and the tumour endemic equilibrium. The results from this
sensitivity analysis indicate the existence of a critical dose of chemotherapy
above which no further significant reduction in the tumour population can be
observed. Numerical simulations show that a successful combinational therapy of
the chemotherapeutic drugs and viruses depends mostly on the virus burst size,
infection rate, and the amount of drugs supplied. Optimal control analysis was
performed, by means of Pontryagin's principle, to further refine predictions of
the model with constant treatment rates by accounting for the treatment costs
and sides effects.

Optimization and Control;Cell Behavior