In the present paper, we address by means of mathematical modeling the following main
question: How can oncolytic virus infection of some normal cells in the vicinity of tumor cells
enhance oncolytic virotherapy? We formulate a mathematical model describing the interactions
between the oncolytic virus, the tumor cells, the normal cells, and the antitumoral and
antiviral immune responses. The model consists of a system of delay differential equations
with one (discrete) delay. We derive the model's basic reproductive number within tumor
and normal cell populations and use their ratio as a metric for virus tumor-specificity. Numerical
simulations are performed for different values of the basic reproduction numbers and
their ratios to investigate potential trade-offs between tumor reduction and normal cells
losses. A fundamental feature unravelled by the model simulations is its great sensitivity to
parameters that account for most variation in the early or late stages of oncolytic virotherapy.
From a clinical point of view, our findings indicate that designing an oncolytic virus that
is not 100% tumor-specific can increase virus particles, which in turn, can further infect
tumor cells. Moreover, our findings indicate that when infected tissues can be regenerated,
oncolytic viral infection of normal cells could improve cancer treatment.
S1 Text. Supplemental information. Contents: 1) Parameter estimation. 2) Model Basic
Reproductive Number. 3) Stability analysis of the virus free steady states. 4) MATLAB Syntax
for the ODE system counterpart of the model.