Designing and building oncolytic viruses

Maroun, Justin; Muñoz-Alía, Miguel; Ammayappan, Arun; Schulze, Autumn; Peng, Kah-Whye; Russell, Stephen

Limiting the pathogenic potential of OVs can also be accomplished by enhancing the host innate immune response. VSV has been engineered to express IFN-β, which induces an antiviral state and reduces proliferation of cells. Cells capable of responding to interferon signaling will limit viral replication in response to the virally produced interferon, further restricting viral replication to tumors with defective innate responses [188] . The expression of IFN-β from infected tumor cells can also prevent off-target infection of nearby tissue through paracrine signaling. Another way to achieve a similar effect is mutating the VSV matrix protein, which is responsible for limiting cellular production of type I interferons [189] . This, and similar approaches, to inactivate viral genes that combat innate immunity has been extensively utilized in the OV field, across a broad range of viral families. Sensitization of OVs to innate immune responses can limit off-target infections and enhance tumor-specific tropism while increasing the therapeutic index.