The mechanisms of genetically modified vaccinia viruses for the treatment of cancer

•We provide an overview of the use of genetically modified VACVs for the treatment of cancer.•VACVs have an inherent affinity toward malignant cells.•Genetic modifications to VACVs have improved tumor cell selectivity and death.•Some modified VACVs are in clinical trials with preliminary results being favorable.•Continued work will be needed to explore the utility of additional VACVs as chemotherapeutics.

The use of oncolytic viruses for the treatment of cancer is an emerging field of cancer research and therapy. Oncolytic viruses are designed to induce tumor specific immunity while replicating selectively within cancer cells to cause lysis of the tumor cells.While there are several forms of oncolytic viruses, the use of vaccinia viruses for oncolysis may be more beneficial than other forms of oncolytic viruses. For example, vaccinia viruses have been shown to exert their anti-tumor effects through genetic engineering strategies which enhance their therapeutic efficacy. This paper will address some of the most common forms of genetically modified vaccinia viruses and will explore the mechanisms whereby they selectively target, enter and destroy cancer cells. Furthermore, this review will highlight how vaccinia viruses activate host immune responses against cancer cells and will address clinical trials evaluating the tumor-directed and killing efficacy of these viruses against solid tumors.