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Myxoma virus therapy of human embryonal rhabdomyosarcoma in a nude mouse model

Authors Kinn V, Hilgenberg V, MacNeill AL

Received 30 April 2016

Accepted for publication 15 June 2016

Published 8 August 2016 Volume 2016:5 Pages 59—71


Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 3

Editor who approved publication: Dr Faris Farassati

Veronica G Kinn, Valerie A Hilgenberg, Amy L MacNeill

Department of Microbiology, Immunology and Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO, USA

Abstract: Rhabdomyosarcoma (RMS) is a devastating tumor of young people that is difficult to cure. To determine if oncolytic virus therapy can improve outcomes in individuals with RMS, myxoma virus expressing a red fluorescent protein (MYXV-red) was evaluated for antitumoral effects using a murine model of RMS. Fluorescent protein was expressed in four RMS cell lines inoculated with MYXV-red, indicating that these cells were semipermissive to MYXV infection. MYXV-red replication and cytopathic effects were further evaluated using human embryonal RMS (CCL-136) cells. Logarithmic growth of MYXV-red and significant cell death were observed 72 hours after inoculation with MYXV. The oncolytic effects of MYXV-red were then studied in nude mice that were injected subcutaneously with CCL-136 cells to establish RMS xenografts. Once tumors measured 5 mm in diameter, mice were treated with multiple intratumoral injections of MXYV-red or saline. The average final tumor volume and rate of tumor growth were significantly decreased, and median survival time was significantly increased in MYXV-red-treated mice (P-values =0.0416, 0.0037, and 0.0004, respectively). Histologic sections of MYXV-red-treated tumors showed increased inflammation compared to saline-treated tumors (P-value =0.0002). In conclusion, MXYV-red treatment of RMS tumors was successful in individual mice as it resulted in decreased tumor burden in eight of eleven mice with nearly complete tumor remission in five of eleven mice. These data hold promise that MYXV-red treatment may be beneficial for people suffering from RMS. To our knowledge, this is the first report of successful treatment of RMS tumors using an oncolytic poxvirus.

Keywords: poxvirus, myxoma virus, oncolytic virus, rhabdomyosarcoma

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