Bistability in a model of tumor-immune system interactions with an oncolytic viral therapy.

ABSTRACT

A mathematical model of tumor-immune system interactions with an oncolytic virus therapy for which the immune system plays a twofold role against cancer cells is derived. The immune cells can kill cancer cells but can also eliminate viruses from the therapy. In addition, immune cells can either be stimulated to proliferate or be impaired to reduce their growth by tumor cells. It is shown that if the tumor killing rate by immune cells is above a critical value, the tumor can be eradicated for all sizes, where the critical killing rate depends on whether the immune system is immunosuppressive or proliferative. For a reduced tumor killing rate with an immunosuppressive immune system, that bistability exists in a large parameter space follows from our numerical bifurcation study. Depending on the tumor size, the tumor can either be eradicated or be reduced to a size less than its carrying capacity. However, reducing the viral killing rate by immune cells always increases the effectiveness of the viral therapy. This reduction may be achieved by manipulating certain genes of viruses via genetic engineering or by chemical modification of viral coat proteins to avoid detection by the immune cells.