The Current Status and Future Prospects of Oncolytic Viruses in Clinical Trials against Melanoma, Glioma, Pancreatic, and Breast Cancers

Abstract

Oncolytic viral therapy has been accepted as a standard immunotherapy since talimogene laherparepvec (T-VEC, Imlygic®) was approved by the Food and Drug Administration (FDA) and European Medicines Agency (EMA) for melanoma treatment in 2015. Various oncolytic viruses (OVs), such as HF10 (Canerpaturev—C-REV) and CVA21 (CAVATAK), are now actively being developed in phase II as monotherapies, or in combination with immune checkpoint inhibitors against melanoma. Moreover, in glioma, several OVs have clearly demonstrated both safety and a promising efficacy in the phase I clinical trials. Additionally, the safety of several OVs, such as pelareorep (Reolysin®), proved their safety and efficacy in combination with paclitaxel in breast cancer patients, but the outcomes of OVs as monotherapy against breast cancer have not provided a clear therapeutic strategy for OVs. The clinical trials of OVs against pancreatic cancer have not yet demonstrated efficacy as either monotherapy or as part of combination therapy. However, there are several oncolytic viruses that have successfully proved their efficacy in different preclinical models. In this review, we mainly focused on the oncolytic viruses that transitioned into clinical trials against melanoma, glioma, pancreatic, and breast cancers. Hence, we described the current status and future prospects of OVs clinical trials against melanoma, glioma, pancreatic, and breast cancers.

Replicative conditioning of Herpes simplex type 1 virus by Survivin promoter, combined to ERBB2 retargeting, improves tumour cell-restricted oncolysis

“…Since T-VEC approval in 2015 for the treatment of advanced-stage unresectable melanoma, several oncolytic viruses have successfully proved their safety and efficacy in different preclinical models and are currently under clinical evaluations 29,30,50 . Nevertheless, emerging evidences suggest that there is still room for improvements of oncolytic virotherapy through combination therapies (e.g.…”

Immunotherapy: A Challenge of Breast Cancer Treatment

“…Among the different approaches that are currently being considered and despite their limited efficacy when delivered as a monotherapy [99], oncolytic viruses have demonstrated their safety [100] and ability in targeting and killing cancer cells as well as in stimulating immunotherapeutic effects in patients [101], positioning themselves as a promising strategy to increase treatment efficacy when used in combination therapy [99][100][101] and as a unique platform for personalized treatment of patients with advanced breast cancer [101].…”

A Triple-Regulated Oncolytic Adenovirus Carrying MicroRNA-143 Exhibits Potent Antitumor Efficacy in Colorectal Cancer

“…13 Recently, oncolytic adenoviruses have been commonly used in clinical trials for cancer gene therapy. 14,15 Among them, the cancer-targeting gene virotherapy (CTGVT) strategy 16 might be a useful strategy for the treatment of advanced or metastatic cancer. For example, inserting the vascular endothelial cell growth inhibitor (VEGI) into a selectively replicating adenovirus with an E1B-55kDa gene deletion (ZD55) to construct ZD55-VEGI-251 leads to a much more severe cytopathic effect than control viruses on human cancer cell line HeLa, hepatoma cell line SMMC-7721, and CRC cell line SW620.…”