A comparative study of the replicative properties of antitumor recombinant vaccinia viruses in cultivated U87 human glioblastoma cells and simian CV-1 kidney cells

Abstract

At present, virotherapy is one of the rapidly developing areas in the treatment of cancer, and its advantage is the selective destruction of cancer cells with the minimal destructive effect on the healthy cells of the body. Orthopoxviruses provide a promising basis for the design of oncolytic drugs. They have a number of advantages over other viral vectors, and one of these advantages is the large capacity of their genomes. It allows them to be furnished with genes encoding proteins with antitumor properties. In this study, we compare the replicative properties of ten variants of the vaccinia virus (LIVP strain of VACV) tested on cultures of human glioblastoma cells and simian CV-1 kidney cells. Some of these viruses have additional genes, such as those encoding the granulocyte-macrophage colony-stimulating factor, apoptosis-inducing protein TRAIL, and green fluorescent protein. We have also studied VACV with five virulence genes deleted, namely, the genes encoding hemagglutinin, the γ-interferon-binding protein, thymidine kinase, the complement-binding protein, and the Bcl2-like inhibitor of apoptosis. The reactogenicity and neurovirulence of this disarmed derivative are much less than in the original LIVP strain. It has been found that derivatives of the vaccinia virus with the deleted thymidine kinase gene most intensely replicate in the glioblastoma cell culture.