Oncolytic virus therapy in cancer: A current review

Figure 1 Mechanism of action of oncolytic viruses. Initially, oncolytic viruses can be administered by different pathways, such as intratumoral, subcutaneous, intraperitoneal, and intrathecal. Natural tropism and genetic targeting are responsible for favoring the arrival of oncolytic viruses to the tumor cells. Thereafter, the oncolytic viruses start to recognize the abnormal cells through substances expressed in the tumor environment and can use different receptors to connect and infect the host cell. From this point, the virus starts to use the cellular machinery for its replication process, producing viral proteins, reducing the cell function, stimulating oxidative stress states and contributing to the activation of some pathways related to the autophagic processes. At the same time, the antigen-presenting cells encompass some viral organisms, generating the formation of an endosomal vesicle that will merge with a lysosomal vesicle and will cause the digestion of the virus, providing smaller viral particles to be processed inside the cell. Later, the expression of the major histocompatibility complex class 2 together with the viral proteins on the cell surface occurs, creating a favorable environment for the antigenic presentation and subsequent activation and stimulation of the CD4+ T cells and CD8+ T cells, the first related to the production of cytokines responsible for contributing to the migration and maturation processes of inflammatory cells, and the second related to the direct action against the infected cells. Finally, the viral action and the immune response contribute to the destruction of the tumor cells releasing the viral progeny in the host organism allowing it to infect other abnormal cells and restart the process of combatting the tumor. Furthermore, cell death also releases tumor antigens that the immune system can identify, contributing to the formation of new inflammatory responses capable of acting both in the tumor environment and even in metastatic sites.