Human Rhinoviruses: a novel class of oncolytic virus

Abstract

While continuing to develop new and improved OVs, researchers have been vigilant in optimizing their ability to safely infect, replicate, and induce an immune response within tumors. There are currently two crucial limitations in OV development, however: modification of viruses often negatively impact their ability to infect, and induction of strong immune responses also promotes rapid viral clearance. In this study, we investigate wild-type HRVs as a novel class of OV. Multiple HRV serotypes were propagated in human melanoma cell lines to produce highly oncolytic populations of virus. A large panel of cancer types were infected, with cytotoxicity evaluated using flow cytometry and real time live imaging. Pro-inflammatory signaling was assessed by cytokine multiplexing. Tumor responses to HRV were assessed in human xenograft and in syngeneic, immune-competent mouse tumor models. We find that HRVs are capable of infecting and killing a wide variety of human cancer cell lines in vitro and in vivo, inducing pro-inflammatory responses and, ultimately, tumor regression. We propose that the natural safety profile of these viruses, coupled with their anti-tumor efficacy and multivalent potential seen in our preclinical model systems, make HRVs ideal candidates for development as oncolytic viruses for clinical testing. Simple SummaryThe idea of utilizing viruses to combat cancer has been around for over a century, yet in practice has seen relatively modest therapeutic success following decades of strategic design to improve safety, efficacy, and tumor selectivity. Engagement of an immune response is critical to have lasting tumor regression upon treatment, but many patients are unable to mount a sufficient response to standard-of-care immunotherapy alone. Oncolytic viruses (OVs) have been shown to synergize with such therapies to accomplish this goal to varying degrees. The purpose of this study is to investigate human rhinoviruses (HRVs) to establish their efficacy as a novel class of anti-cancer agents. We aim to use HRVs to promote longer lasting and more effective immune responses to tumors by fostering viral persistence and immune evasion, in addition to developing multivalent treatment strategies that enhance tumor regression by preventing tumor escape from viral infection.