Therapeutic Implementation of Oncolytic Viruses for Cancer Immunotherapy: Review of Challenges and Current Clinical Trials.

The development of cancer therapeutics has evolved from general targets with radiation and chemotherapy and shifted toward treatments with a more specific mechanism of action such as small molecule kinase inhibitors, monoclonal antibodies against tumor antigens, or checkpoint inhibitors. Recently, oncolytic viruses (OVs) have come to the forefront as a viable option for cancer immunotherapy, especially for "cold" tumors, which are known to inhabit an immunologically suppressive tumor microenvironment. Desired characteristics of viruses are selected through genetic attenuation of uncontrolled virulence, and some genes are replaced with ones that enhance conditional viral replication within tumor cells. Treatment with OVs must overcome various hurdles such as premature viral suppression by the host's immune system and the dense stromal barrier. Currently, clinical studies investigate the efficacy of OVs in conjunction with various anti-cancer therapeutics, including radiotherapy, chemotherapy, immune checkpoint inhibitors, and monoclonal antibodies. Thus, future research should explore how cancer therapeutics work synergistically with certain OVs in order to create more effective combination therapies and improve patient outcomes.