US EPA

5037153 

Journal Article 

Multi-modal Potentiation of Oncolytic Virotherapy by Vanadium Compounds 

Selman, M; Rousso, C; Bergeron, A; Son, HH; Krishnan, R; El-Sayes, NA; Varette, O; Chen, A; Le Boeuf, F; Tzelepis, F; Bell, JC; Crans, DC; Diallo, JS 

2018 

26 

1 

56-69 

English 

29175158 

10.1016/j.ymthe.2017.10.014 

WOS:000423013500010 

Oncolytic viruses (OV) are an emerging class of anticancer bio-therapeutics that induce antitumor immunity through selective replication in tumor cells. However, the efficacy of OVs as single agents remains limited. We introduce a strategy that boosts the therapeutic efficacy of OVs by combining their activity with immuno-modulating, small molecule protein tyrosine phosphatase inhibitors. We report that vanadium-based phosphatase inhibitors enhance OV infection in vitro and ex vivo, in resistant tumor cell lines. Furthermore, vanadium compounds increase antitumor efficacy in combination with OV in several syngeneic tumor models, leading to systemic and durable responses, even in models otherwise refractory to OV and drug alone. Mechanistically, this involves subverting the antiviral type I IFN response toward a death-inducing and pro-inflammatory type II IFN response, leading to improved OV spread, increased bystander killing of cancer cells, and enhanced antitumor immune stimulation. Overall, we showcase a new ability of vanadium compounds to simultaneously maximize viral oncolysis and systemic anticancer immunity, offering new avenues for the development of improved immunotherapy strategies.