Oncolytic viruses, as novel biological anti-tumor agents, provide anti-tumor therapeutic effects by
different mechanisms including directly selective tumor cell lysis and secondary systemic anti-tumor immune
responses. Some wide-type and genetically engineered oncolytic viruses have been applied in clinical trials.
Among them, T-Vec has a significant therapeutic effect on melanoma patients and received the approval of the
US Food and Drug Administration (FDA) as the first oncolytic virus to treat cancer in the US. However, the
mechanisms of virus interaction with tumor and immune systems have not been clearly elucidated and there are
still no “gold standards” for instructions of virotherapy in clinical trials. This Review collected the recent clinical
trials data from 2005 to summarize the basic oncolytic viruses biology, describe the application in recent clinical
trials, and discuss the challenges in the application of oncolytic viruses in clinical trials.