Oncolytic Viruses on Drugs: Achieving Higher Therapeutic Efficacy.

Over the past 20 years there has been a dramatic expansion in the testing of oncolytic viruses (OVs) for the treatment of cancer. OVs are unique biotherapeutics that induce multimodal responses toward tumors, from direct cytopathic effects on cancer cells, to tumor associated blood vessel disruption, and ultimately potent stimulation of anti-tumor immune activation. These agents are highly targeted and can be efficacious as cancer treatments resulting in some patients experiencing complete tumor regression and even cures from OV monotherapy. However, most patients have limited responses with viral replication in tumors often found to be modest and transient. To augment OV replication, increase bystander killing of cancer cells, and/or stimulate stronger targeted anti-cancer immune responses, drug combination approaches have taken center stage for translation to the clinic. Here we comprehensively review drugs that have been combined with OVs to increase therapeutic efficacy, examining the proposed mechanisms of action, and we discuss trends in pharmaco-viral immunotherapeutic approaches currently being investigated.