Therapy with oncolytic viruses: progress and challenges

Oncolytic viruses (OVs) are an emerging class of cancer therapeutics that offer the benefits of selective replication in tumour cells, delivery of multiple eukaryotic transgene payloads, induction of immunogenic cell death and promotion of antitumour immunity, and a tolerable safety profile that largely does not overlap with that of other cancer therapeutics. Four OVs and one non-oncolytic virus have been approved for cancer treatment globally, although talimogene laherparepvec (T-VEC) remains the only widely approved therapy. T-VEC is indicated for treating patients with recurrent melanoma after initial surgery and was approved in 2015. An expanding body of data on the clinical experience of patients receiving T-VEC is now becoming available, as are data from clinical trials of various other OVs in a range of other cancers. Despite increasing research interest, a better understanding of the underlying biology and pharmacology of OVs is needed to enable these agents' full therapeutic potential in cancer patients. This review summarizes the available data and guides on optimizing the use of OVs in clinical practice, focusing on the clinical experience with T-VEC. In addition, it describes data on selected novel OVs currently in clinical development, either as monotherapies or as part of combination regimens. The outcomes also discuss some of the preclinical, clinical and regulatory hurdles that have thus far limited the development of OVs.