Myxoma virus is a novel oncolytic virus with significant antitumor activity against experimental human gliomas.
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.
Lun
Xueqing
X
Departments of Oncology, Clinical Neurosciences, and Biochemistry and Molecular Biology, University of Calgary, and Tom Baker Cancer Centre, Calgary, Alberta, Canada.|Clark-Smith Integrative Brain Tumour Research Center, Calgary, Alberta, Canada.
Yang
Wenqing
W
Departments of Oncology, Clinical Neurosciences, and Biochemistry and Molecular Biology, University of Calgary, and Tom Baker Cancer Centre, Calgary, Alberta, Canada.
Alain
Tommy
T
Departments of Oncology, Clinical Neurosciences, and Biochemistry and Molecular Biology, University of Calgary, and Tom Baker Cancer Centre, Calgary, Alberta, Canada.|Clark-Smith Integrative Brain Tumour Research Center, Calgary, Alberta, Canada.
Shi
Zhong-Qiao
ZQ
Departments of Oncology, Clinical Neurosciences, and Biochemistry and Molecular Biology, University of Calgary, and Tom Baker Cancer Centre, Calgary, Alberta, Canada.
Muzik
Huong
H
Departments of Oncology, Clinical Neurosciences, and Biochemistry and Molecular Biology, University of Calgary, and Tom Baker Cancer Centre, Calgary, Alberta, Canada.
Barrett
John W
JW
BioTherapeutics Research Group, Robarts Institute and Department of Microbiology and Immunology, University of Western Ontario, London, Ontario, Canada.
McFadden
Grant
G
BioTherapeutics Research Group, Robarts Institute and Department of Microbiology and Immunology, University of Western Ontario, London, Ontario, Canada.
Bell
John
J
Ottawa Regional Cancer Centre, Ottawa, Ontario, Canada.
Hamilton
Mark G
MG
Departments of Oncology, Clinical Neurosciences, and Biochemistry and Molecular Biology, University of Calgary, and Tom Baker Cancer Centre, Calgary, Alberta, Canada.
Senger
Donna L
DL
Departments of Oncology, Clinical Neurosciences, and Biochemistry and Molecular Biology, University of Calgary, and Tom Baker Cancer Centre, Calgary, Alberta, Canada.|Clark-Smith Integrative Brain Tumour Research Center, Calgary, Alberta, Canada.
Forsyth
Peter A
PA
Departments of Oncology, Clinical Neurosciences, and Biochemistry and Molecular Biology, University of Calgary, and Tom Baker Cancer Centre, Calgary, Alberta, Canada.|Clark-Smith Integrative Brain Tumour Research Center, Calgary, Alberta, Canada.
D000818:Animals; D001932:Brain Neoplasms / Q000628:therapy* / Q000821:virology*; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D005260:Female; D005910:Glioma / Q000628:therapy* / Q000821:virology*; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009233:Myxoma virus / Q000502:physiology*; D041681:NIH 3T3 Cells; D050130:Oncolytic Virotherapy / Q000379:methods*; D023041:Xenograft Model Antitumor Assays