Persistent Virus Presence during Experimental Oncolytic Virus Therapy in the Model of Subcutaneous Mouse Xenografts of Human Glyobolastoma Multiforme

The approach of using oncolytic viruses for the therapy of malignant diseases is considered as a promising alternative to cytotoxic chemotherapy. Especially relevant is the development of new therapies in the case of malignant glioblastomas, a disease against which effective treatments have not been developed to date. Viruses of many different families demonstrate selective activity against glioblastoma cells. In particular, a pronounced lytic activity against glioblastomas demonstrate nonpathogenic or vaccine strains of human enteroviruses. The main mechanism of oncolytic action of enteroviruses is associated with their ability to selectively replicate in tumor cells, although stimulation of the immune system also contributes to the oncolytic effect. The objective of the study was to determine the possibility of effective delivery of oncolytic enterovirus (vaccine strain type 1 poliovirus) to the subcutaneous xenografts of the human glioblastoma cell line (U87MG) and to determine the dynamics of viral oncolysis and the presence of the introduced virus in the body of tumor-bearing immunodeficient mice. It was found that in this experimental model, the delivery of the virus to the tumor is possible with the intravenous virus dose as low as 105 pfu. A single administration of the virus led to a gradual regression of tumors, while the virus was detectable in the blood of mice. However, the virus could no longer be detected two days after the tumor disappeared. The presence of the virus and the start of the virus regression process were accompanied by a significant increase in the survival rate of mice. According to the results of the study, it can be concluded that in the absence of a significant immune component, effective tumor oncolysis can occur through direct oncolytic action of enterovirus