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Published on: October 30, 2016
Features of the Antitumor Effect of Vaccinia Virus Lister Strain
Evgeniy Zonov1, Galina Kochneva2, Anastasiya Yunusova3
1Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences (ICBFM SB RAS), 8 Lavrentiev Avenue, Novosibirsk 630090, Russia. zoman89@gmail.com.
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.
Insights
Genetically unmodified vaccinia virus (VACV) shows antitumor effects through direct tumor cell destruction and by suppressing tumor cell division. This study investigated the natural oncolytic properties of the L-IVP strain of VACV.
Area of Science:
- Oncology
- Virology
- Cancer Research
Background:
- Vaccinia virus (VACV) has been explored for cancer treatment, primarily through engineered strains.
- The intrinsic oncolytic capabilities of unmodified VACV strains require further investigation.
Purpose of the Study:
- To investigate the antitumor mechanisms of the genetically unmodified L-IVP strain of vaccinia virus.
- To understand how VACV exerts its effects on different types of tumors.
Main Methods:
- Intratumoral injection of VACV L-IVP strain into human A431 carcinoma xenografts and murine Ehrlich carcinoma models.
- Utilized virological assays, immunohistochemistry, and light and electron microscopy.
Main Results:
- The L-IVP strain was detected in visceral organs but cleared rapidly from the bloodstream.
- VACV L-IVP reduced tumor size in both models, employing distinct mechanisms.
- Direct viral replication and cell lysis were key in A431 carcinoma regression.
- In Ehrlich carcinoma, VACV L-IVP suppressed tumor cell mitosis by inducing S-phase arrest.
Conclusions:
- Genetically unmodified VACV possesses dual antitumor mechanisms: direct oncolysis and cell cycle suppression.
- The L-IVP strain of VACV demonstrates potential as a natural oncolytic agent.
- VACV's efficacy and mechanism depend on the tumor type and viral replication efficiency.
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