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

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.

Developing Picornaviruses for Cancer Therapy

“…Rigvir has shown toxicity in vitro against a broad range of cell lines, including melanoma, pancreatic adenocarcinoma, muscle rhabdomyosarcoma, mesenchymal stem cells, gastric carcinoma, lung carcinoma and human normal dermal fibroblasts [63].…”

Human Neonatal Fc Receptor Is the Cellular Uncoating Receptor for Enterovirus B

“…RIGVIR, the Echo 7-based oncolytic drug, has been approved for clinical use in Latvia for melanoma treatment (Chumakov et al, 2012;Donin ‚ a et al, 2015). However, the lack of receptor information for Echo 7 hampered our understanding and evaluation of this type of oncolytic therapy (Chumakov et al, 2012;Tilgase et al, 2018). The discovery of FcRn as its receptor will improve the development of echovirus-based oncolytic therapeutics.…”

Management of a primary malignant melanoma of uterine cervix stage IVA patient with radical surgery and adjuvant oncolytic virus Rigvir® therapy: A case report

“…1,4 The oncolytic virus Rigvir ® has shown effectiveness in vitro and in a retrospective study improved the clinical outcome in skin melanoma. 11,12 The present case suggests that oncolytic virotherapy might also be beneficial to study as adjuvant treatment in primary malignant melanoma of uterine cervix.…”