Designing and building oncolytic viruses

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

Each step of the above process can be impacted by virus engineering. Not only can the kinetics and mode of cell killing be manipulated (see the previous section on virus spread), but also the OVs can be armed with a wide variety of immunoregulatory genes whose products will be secreted into the interstitial fluid space. Thus, OVs have been engineered to express the following: high levels of type I interferons to better drive the early innate/inflammatory response; GM-CSF to stimulate the phagocytic activity and lymph node trafficking of professional antigen presenting cells; chemokines to enhance the IT recruitment of immune and inflammatory effector cells, especially cytotoxic T cells; cytokines to drive the activation and proliferation of tumor-resident cytotoxic T cells; bispecific T-cell engagers to enable tumor cell killing by T cells not recognizing tumor antigens; checkpoint inhibitor antibodies to block the protective PD-L1/B7.1 shield that protects tumor cells from T-cell attack; cytokines to increase MHC-peptide neoantigen expression on uninfected tumor cells; or cloned tumor antigens to further amplify tumor-specific immunity [165] .