Review: Oncolytic virotherapy, updates and future directions

Abstract

Oncolytic viruses (OVs) are viral strains that can infect and kill malignant cells while spare their normal counterparts. OVs can access cells through binding to receptors on their surface or through fusion with the plasma membrane and establish a lytic cycle in tumors, while leaving normal tissue essentially unharmed. Multiple viruses have been investigated in humans for the past century. IMLYGIC™ (T-VEC/Talimogene Laherparepvec), a genetically engineered Herpes Simplex Virus, is the first OV approved for use in the United States and the European Union for patients with locally advanced or non-resectable melanoma.Although OVs have a favorable toxicity profile and are impressively active anticancer agents in vitro and in vivo the majority of OVs have limited clinical efficacy as a single agent. While a virus-induced antitumor immune response can enhance oncolysis, when OVs are used systemically, the antiviral immune response can prevent the virus reaching the tumor tissue and having a therapeutic effect. Intratumoral administration can provide direct access to tumor tissue and be beneficial in reducing side effects.Immune checkpoint stimulation in tumor tissue has been noted after OV therapy and can be a natural response to viral-induced oncolysis. Also for immune checkpoint inhibition to be effective in treating cancer, an immune response to tumor neoantigens and an inflamed tumor microenvironment are required, both of which treatment with an OV may provide. Therefore, direct and indirect mechanisms of tumor killing provide rationale for clinical trials investigating the combination of OVs other forms of cancer therapy, including immune checkpoint inhibition.

The Role of Oncolytic Viruses in the Treatment of Melanoma

“…(1, 2) Over the past several years, there has been an intensification of laboratory, pre-clinical, and clinical research in the field of oncolytic virotherapy, culminating in over 40 clinical trials involving OVs recruiting patients in 2017.…”

Enhancing Antitumor Efficacy of Heavily Vascularized Tumors by RAMBO Virus through Decreased Tumor Endothelial Cell Activation

“…Various oncolytic viruses (OVs) including oHSV can infect and lyse proliferating tumor cells and endothelial cells, resulting in reduced perfusion and anti-angiogenic effects [17,26,27]. However, we and others have uncovered that OV treatment induces secretion of VEGF and IL-8 in the tumor microenvironment (TME), thereby increasing angiogenesis in residual tumors after virus clearance [28][29][30].…”

Toll‐like receptors as novel therapeutic targets for herpes simplex virus infection

“…Natural neurotropism has led to the development of HSV‐based vectors for neuronal gene delivery. Now, versatile and high titer HSV‐based gene vectors are designed and implemented in the therapeutic and prophylactic settings to attack infectious diseases and cancer, possibly improving the efficiency of gene targeted molecules like naked siRNA or even serving for new generation genome editing tools like CRISPR/Cas …”