Seminar - Chemistry Department
Vanadium Compounds in Oncolytic Virotherapy
Debbie Crans, Colorado State
Oncolytic viruses are an emerging class of anticancer bio-therapeutics that induce antitumor immunity through selective replication in tumor cells.1,2 The efficacy of oncolytic viruses as single agents can however be improved and we have developed a strategy that boosts the therapeutic efficacy of oncolytic viruses by combining their activity with immuno-modulating, and small molecule protein tyrosine phosphatase inhibitors. The possibility that the phosphatase inhibition by vanadium compounds3,4 may be relevant to these studies are investigated. Since vanadium are potent phosphatase inhibitors, and their inhibition is attributed to the favorable five-coordinate geometry of phosphate ester hydrolysis transition states much of the research carried out in this area can be used in studies with oncolytic viruses. The chemistry that vanadium compounds undergo under physiological conditions are continuously examined.5 Specifically, chemical speciation studies are important to development of new vanadium compounds.5 Recent data mining studies led to a better understanding of the key aspects of inhibition of phosphatases and future inhibitor development. We found that vanadium-based phosphatase inhibitors could enhance oncolytic viruses’ infection in vitro and ex vivo, in resistant tumor cell lines. Furthermore, vanadium compounds increased anti-tumor efficacy in combination with oncolytic viruses in several syngeneic tumor models, leading to systemic and durable responses, even in models otherwise refractory to oncolytic viruses and drug alone.
In summary, we introduce a strategy that boost the therapeutic efficacy of oncolytic viruses by combining their activity with immuno-modulating small molecules protein tyrosine phosphatase inhibitors. Overall, we present studies on the novel ability of vanadium-based compounds to simultaneously maximize viral oncolytic and systemic anticancer immunity, offering new avenues for the development of improved immunotherapy strategies.