J Cancer 2018; 9(6):1033-1049. doi:10.7150/jca.23242

Research Paper

Effect of the oncolytic ECHO-7 virus Rigvir® on the viability of cell lines of human origin in vitro

Andra Tilgase1✉, Liene Patetko2, Ilze Blāķe2, Anna Ramata‑Stunda2, Mārtiņš Borodušķis2, Pēteris Alberts1

1. International Virotherapy Center, Riga, Latvia
2. Faculty of Biology, University of Latvia, Riga, Latvia

Abstract

Background: The role of oncolytic viruses in cancer treatment is increasingly studied. The first oncolytic virus (Rigvir®, ECHO-7) was registered in Latvia over a decade ago. In a recent retrospective study Rigvir® decreased mortality 4.39-6.57-fold in stage IB-IIC melanoma patients. The aims of the present study are to test the effect of Rigvir® on cell line viability in vitro and to visualize the cellular presence of Rigvir® by immunocytochemistry.

Methods: The cytolytic effect of Rigvir® on the viability of FM-9, RD, AGS, A549, HDFa, HPAF‑II, MSC, MCF7, HaCaT, and Sk-Mel-28 cell lines was measured using live cell imaging. PBMC viability was measured using flow cytometry. The presence of ECHO-7 virus was visualized using immunocytochemistry. Statistical difference between treatment groups was calculated using two-way ANOVA.

Results: Rigvir® (10%, volume/volume) reduced cell viability in FM-9, RD, AGS, A549, HDFa, HPAF‑II and MSC cell lines by 67-100%. HaCaT cell viability was partly affected while Rigvir® had no effect on MCF7, Sk-Mel-28 and PBMC viability. Detection of ECHO-7 by immunocytochemistry in FM-9, RD, AGS, A549, HDFa, HPAF-II and Sk-Mel-28 cell lines suggests that the presence of Rigvir® in the cells preceded or coincided with the time of reduction of cell viability. Rigvir® (10%) had no effect on live PBMC count.

Conclusions: The results suggest that Rigvir® in vitro reduces the viability of cells of human melanoma, rhabdomyosarcoma, gastric adenocarcinoma, lung carcinoma, pancreas adenocarcinoma but not in PBMC. The presence of Rigvir® in the sensitive cells was confirmed using anti-ECHO-7 antibodies. The present results suggest that a mechanism of action for the clinical benefit of Rigvir® is its cytolytic properties. The present results suggest that the effect of Rigvir® could be tested in other cancers besides melanoma. Further studies of possible Rigvir® entry receptors are needed.

Keywords: ECHO-7 virus, immunocytochemistry, oncolytic virus, cell viability, Rigvir.

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How to cite this article:
Tilgase A, Patetko L, Blāķe I, Ramata‑Stunda A, Borodušķis M, Alberts P. Effect of the oncolytic ECHO-7 virus Rigvir® on the viability of cell lines of human origin in vitro. J Cancer 2018; 9(6):1033-1049. doi:10.7150/jca.23242. Available from http://www.jcancer.org/v09p1033.htm