Modeling oncolytic virotherapy: is complete tumor-tropism too much of a good thing?

The specific targeting of tumor cells by replication-competent oncolytic viruses is considered indispensable for realizing the potential of oncolytic virotherapy. Yet off-target infections by oncolytic viruses may increase virus production, further reducing tumor load. This ability may be critical when tumor-cell scarcity or the onset of an adaptive immune response constrain viral anti-tumoral efficacy. Here we develop a mathematical framework for assessing whether oncolytic viruses with reduced tumor-specificity can more effectively eliminate tumors while keeping losses to normal cell populations low. We find viruses that infect some normal cells can potentially balance the competing goals of tumor elimination and minimizing the effects on normal cell populations. Particularly when infected tissues can be regenerated, moderating rather than completely eliminating the ability of oncolytic viruses to infect and lyse normal cells could improve cancer treatment, with potentially fewer side-effects than conventional treatments such as chemotherapy.