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Oncolytic Efficacy of Recombinant Vesicular Stomatitis Virus and Myxoma Virus in Experimental Models of Rhabdoid Tumors

Authors' Affiliations: ¹ Departments of Oncology, Clinical Neurosciences, and Biochemistry and Molecular Biology, University of Calgary, the Tom Baker Cancer Centre, and the Clark H. Smith Brain Tumour Research Centre, Calgary, Alberta, Canada; ² Medical Research Center, Fuzhou General Hospital, Fuzhou, China; ³ Ottawa Regional Cancer Centre Research Laboratories, Ottawa, Ontario, Canada; ⁴ BioTherapeutics Research Group, Robarts Research Institute and Department of Microbiology and Immunology, University of Western Ontario, London, Ontario, Canada; ⁵ Department of Molecular Genetics and Microbiology, University of Florida, Gainesville, Florida; and ⁶ Division of Human Genetics, Department of Pediatrics, The Children's Hospital of Philadelphia and the University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania

Requests for reprints: Peter A. Forsyth, Clark H. Smith Brain Tumour Research Centre, Southern Alberta Cancer Research Institute, Room 2AA19 Health Research Innovation Centre, 3330 Hospital Drive NW, Calgary, Alberta, Canada T2N 4N1. Phone: 403-210-3934; Fax: 403-210-8135; E-mail: pforsyth{at}ucalgary.ca.

Purpose: Rhabdoid tumors are highly aggressive pediatric tumors that are usually refractory to available treatments. The purpose of this study was to evaluate the therapeutic potential of two oncolytic viruses, myxoma virus (MV) and an attenuated vesicular stomatitis virus (VSV^M51), in experimental models of human rhabdoid tumor.

Experimental Design: Four human rhabdoid tumor cell lines were cultured in vitro and treated with live or inactivated control virus. Cytopathic effect, viral gene expression, infectious viral titers, and cell viability were examined at various time points after infection. To study viral oncolysis in vivo, human rhabdoid tumor cells were implanted s.c. in the hind flank or intracranially in CD-1 nude mice and treated with intratumoral (i.t.) or i.v. injections of live or UV-inactivated virus. Viral distribution and effects on tumor size and survival were assessed.

Results: All rhabdoid tumor cell lines tested in vitro were susceptible to productive lethal infections by MV and VSV^M51. I.t. injection of live MV or VSV^M51 dramatically reduced the size of s.c. rhabdoid tumor xenografts compared with control animals. I.v. administration of VSV^M51 or i.t. injection of MV prolonged the median survival of mice with brain xenografts compared with controls (VSV^M51: 25 days versus 21 days, log-rank test, P = 0.0036; MV: median survival not reached versus 21 days, log-rank test, P = 0.0007). Most of the MV-treated animals (4 of 6; 66.7%) were alive and apparently "cured" when the experiment was arbitrarily ended (>180 days).

Conclusions: These results suggest that VSV^M51 and MV could be novel effective therapies against human rhabdoid tumor.