Combining of Oncolytic Virotherapy and Other Immunotherapeutic Approaches in Cancer: A Powerful Functionalization Tactic

Oncolytic viruses have found a good place in the treatment of cancer. Administering oncolytic viruses directly or by applying genetic changes can be effective in cancer treatment through the lysis of tumor cells and, in some cases, by inducing immune system responses. Moreover, oncolytic viruses induce antitumor immune responses via releasing tumor antigens in the tumor microenvironment (TME) and affect tumor cell growth and metabolism. Despite the success of virotherapy in cancer therapies, there are several challenges and limitations, such as immunosuppressive TME, lack of effective penetration into tumor tissue, low efficiency in hypoxia, antiviral immune responses, and off‐targeting. Evidence suggests that oncolytic viruses combined with cancer immunotherapy‐based methods such as immune checkpoint inhibitors and adoptive cell therapies can effectively overcome these challenges. This review summarizes the latest data on the use of oncolytic viruses for the treatment of cancer and the challenges of this method. Additionally, the effectiveness of mono, dual, and triple therapies using oncolytic viruses and other anticancer agents has been discussed based on the latest findings. Combining oncolytic viruses with anti‐checkpoint antibodies such as anti‐PD‐1, anti‐PDL‐1, and anti‐CTLA4 or CAR‐T cells can be effective in cancer therapy in a synergistic fashion. Oncolytic virotherapy induces the expression of PD‐1 and PDL‐1 in the tumor microenvironment components. Virotherapy promotes the infiltration of CD4+ and CD8+ T cells into the tumor tissue.