Two is better than one: Complementing oncolytic virotherapy with gemcitabine to potentiate antitumor immune responses

Abstract

Oncolytic viruses (OVs) preferentially infect and kill cancer cells. Additionally, OV-induced immune responses subvert cancer-associated immunosuppression and promote antitumor immunity. We have recently demonstrated that the complementation of oncolytic virotherapy with gemcitabine accentuates its immunostimulatory effects, hence exerting superior antineoplastic activity.

Keywords: MDSCs; antitumor immunity; gemcitabine; immune evasion; oncolytic virus; reovirus; tumor microenvironment.

Figure 1. Gemcitabine potentiates oncolytic virotherapy-induced antitumor immune responses. Reovirus-based virotherapy and gemcitabine primarily target cancer cells by mediating direct oncolytic and pro-apoptotic effects, respectively. In addition, both these interventions promote immunological events that support the development of beneficial antitumor immunity. Interestingly, the addition of gemcitabine to reovirus-based oncolytic virotherapy further potentiates reovirus-induced antitumor immune responses. Thus, the combination of reovirus and gemcitabine produces better cancer outcomes as compared with the either therapeutic intervention alone.