Oncolytic Viruses: Newest Frontier for Cancer Immunotherapy

Abstract

Cancer remains a leading cause of death worldwide. Despite many signs of progress, currently available cancer treatments often do not provide desired outcomes for too many cancers. Therefore, newer and more effective therapeutic approaches are needed. Oncolytic viruses (OVs) have emerged as a novel cancer treatment modality, which selectively targets and kills cancer cells while sparing normal ones. In the past several decades, many different OV candidates have been developed and tested in both laboratory settings as well as in cancer patient clinical trials. Many approaches have been taken to overcome the limitations of OVs, including engineering OVs to selectively activate anti-tumor immune responses. However, newer approaches like the combination of OVs with current immunotherapies to convert "immune-cold" tumors to "immune-hot" will almost certainly improve the potency of OVs. Here, we discuss strategies that are explored to further improve oncolytic virotherapy.

Keywords: cancer therapy; combination therapy; immunotherapy; oncolytic; oncolytic virus; virotherapy.

Figure 1

Therapeutic features of oncolytic virotherapy and ways to improve it. Multiple steps are involved in successful oncolytic virotherapy. First, the virus must be delivered successfully to the tumor bed or TME using an optimized delivery method. Second, the OV must replicate and spread efficiently in the tumor bed, causing oncolysis and release of tumor selective immune stimulating molecules. Third, the OV must function as an immunotherapeutic agent to activate strong innate and adaptive anti-tumor immune responses. All these steps can be further improved by engineering OVs to express suitable transgenes and by combination with other agents or therapies. TME, tumor microenvironment; DAMPS, danger associated molecular patterns; PAMPs, pathogen associated molecular patterns; ICD, immunological cell death; MSCs, Mesenchymal stem cells; NSCs, neural stem cells; ICIs, immune checkpoint inhibitors; TAAs, tumor associated antigens.