Abstract
Oncolytic abilities of vaccinia virus (VACV) served as a basis for the development of various recombinants for treating cancer; however, “natural” oncolytic properties of the virus are not examined in detail. Our study was conducted to know how the genetically unmodified L-IVP strain of VACV produces its antitumor effect. Human A431 carcinoma xenografts in nude mice and murine Ehrlich carcinoma in C57Bl mice were used as targets for VACV, which was injected intratumorally. A set of virological methods, immunohistochemistry, light and electron microscopy was used in the study. We found that in mice bearing A431 carcinoma, the L-IVP strain was observed in visceral organs within two weeks, but rapidly disappeared from the blood. The L-IVP strain caused decrease of sizes in both tumors, however, in different ways. Direct cell destruction by replicating virus plays a main role in regression of A431 carcinoma xenografts, while in Ehrlich carcinoma, which poorly supported VACV replication, the virus induced decrease of mitoses by pushing tumor cells into S-phase of cell cycle. Our study showed that genetically unmodified VACV possesses at least two mechanisms of antitumor effect: direct destruction of tumor cells and suppression of mitoses in tumor cells.
Highlights
The vaccinia virus (Poxviridae family) is among the most “famous” viruses; it is primarily known for its successful use in vaccination and its role in smallpox eradication [1]
For better understanding of the L-IVP strain’s oncolytic abilities, we examined the selectivity of viral lytic effect in normal, diploid and cancer cell lines (Figure 1)
Vaccinia virus (VACV) when we studied the antitumor effects of apoptin-expressing recombinant toward A431 human adenocarcinoma xenografts in comparison with parental the L-IVP strain
Summary
The vaccinia virus (Poxviridae family) is among the most “famous” viruses; it is primarily known for its successful use in vaccination and its role in smallpox eradication [1]. Its ability to kill cancer cells is one of the fundamental biological properties of VACV, and was first reported by Levaditi C. and Nicolau S. in 1923 in the Annals of the Pasteur. Subsequent studies confirmed the oncolytic activity of VACV [3]; over the few decades researchers failed to achieve stable results in treatment of cancer patients using VACV, and most importantly, to avoid complications caused by introducing the infectious virus into human organism. The interest to studies of VACV application in oncology seemed to wane. Progress in genetic engineering enables researchers to change the biological properties of VACV over a wide range, and this has led to a surge of interest to oncolytic abilities of genetically modified VACV
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