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Myxoma Virus Is a Novel Oncolytic Virus with Significant Antitumor Activity against Experimental Human Gliomas

¹ Departments of Oncology, Clinical Neurosciences, and Biochemistry and Molecular Biology, University of Calgary, and Tom Baker Cancer Centre, Calgary, Alberta, Canada; ² BioTherapeutics Research Group, Robarts Institute and Department of Microbiology and Immunology, University of Western Ontario, London, Ontario, Canada; ³ Ottawa Regional Cancer Centre, Ottawa, Ontario, Canada; and ⁴ Clark-Smith Integrative Brain Tumour Research Center, Calgary, Alberta, Canada

Requests for reprints: Peter A. Forsyth, Tom Baker Cancer Center, 1331 29 Street Northwest, Calgary, Alberta, Canada T2N 4N2; E-mail: senger{at}ucalgary.ca.

Myxoma virus, a poxvirus previously considered rabbit specific, can replicate productively in a variety of human tumor cells in culture. The purpose of this study was to determine if there was efficacy or toxicities of this oncolytic virus against experimental models of human malignant gliomas in vitro, in vivo, and ex vivo in malignant glioma specimens. In vitro, the majority of glioma cell lines tested (7 of 8, 87.5%) were fully permissive for myxoma virus replication and killed by infection. In vivo, intracerebral (i.c.) myxoma virus inoculation was well tolerated and produced only minimal focal inflammatory changes at the site of viral inoculation. U87 and U251 orthotopic xenograft models were used to assess myxoma virus efficacy in vivo. A single intratumoral injection of myxoma virus dramatically prolonged median survival compared with treatment with UV-inactivated myxoma virus. Median survival was not reached in myxoma virus-treated groups versus 47.3 days (U87; P = 0.0002) and 50.7 days (U251; P = 0.0027) in UV-inactivated myxoma virus-treated groups. Most myxoma virus-treated animals (12 of 13, 92%) were alive and apparently "cured" when the experiment was finished (>130 days). Interestingly, we found a selective and long-lived myxoma virus infection in gliomas in vivo. This is the first demonstration of the oncolytic activity of myxoma virus in vivo. The nonpathogenic nature of myxoma virus outside of the rabbit host, its capacity to be genetically modified, its ability to produce a long-lived infection in human tumor cells, and the lack of preexisting antibodies in the human population suggest that myxoma virus may be an attractive oncolytic agent against human malignant glioma.

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