Herpes Simplex Virus as Oncolytic Virotherapy : Efficacy and Safety as Monotherapy and in Combination with Anti-PD-1 Inhibitors

Cancer is one of the most complex diseases and it causes millions of deaths worldwide every year. Uncontrolled cell division leads to cancer and can be caused by mutations that are hereditary or acquired. Malignant tumors are metastatic and have invasive capabilities. Melanoma, a type of skin cancer, increases in incidence and mortality every year. Melanoma arises from melanocytes in the skin but can also affect the eyes and mucous. During the past decades survival rates for melanoma patients have improved. If melanoma is detected later on metastasis are more common, and it can affect the lungs, bones and brain. Surgery, chemotherapy and radiation therapy are commonly used treatment methods but they have shown limited effectiveness. New treatments are being explored since the incidence of melanoma is increasing. It is possible to make cancer treatment more personalized by using biological therapies, gene therapy and immunotherapy. Monoclonal antibodies, cancer vaccines, immune checkpoint modulators and oncolytic viruses are examples of biological cancer treatments. Immune checkpoint inhibitors are monoclonal antibodies that can bind to immune cells and enhance their ability to recognize and attack cancer cells. Oncolytic viruses can selectively infect and lyse cancer cells while they do not affect normal cells much. Herpes simplex virus has shown promise in oncolytic virus therapy. It has a large genome which allows modification to increase anticancer resistance and reduce toxicity. Studies have shown that herpes simplex virus can have a positive effect in melanoma patients where surgery is not an option. The aim of this study was to evaluate herpes simplex virus as an oncolytic virus therapy, both as monotherapy and in combination treatments, against melanoma. Clinical studies were searched for in the PubMed database, with the keywords “oncolytic” and “melanoma.” Seven out of the 39 results were relevant and analyzed. Antitumoral effects of oncolytic herpes simplex virus were observed in all studies, though the effect varied. The overall response rate (ORR) was higher in combination therapy studies compared to those with monotherapy. Improved disease control was seen in studies with neoadjuvant treatment, the risk of disease recurrence was reduced by 25 % according to one study and the risk of death was reduced by 51 %. Two studies showed effects in advanced melanoma. More than 80% of patients in all studies experienced side effects, though they were generally mild to moderate. Severe side effects were observed but were rare. Although there were indications that oncolytic herpes simplex virus may be effective in melanoma treatment, many of the results were not statistically significant. Additional and larger randomized studies are needed to further evaluate the effect and to identify patient subgroups that may respond better to treatment.