Oncolytic efficacy of recombinant vesicular stomatitis virus and myxoma virus in experimental models of rhabdoid tumors.
OBJECTIVE
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(DeltaM51)), in experimental models of human rhabdoid tumor.


METHODS
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(DeltaM51). I.t. injection of live MV or VSV(DeltaM51) dramatically reduced the size of s.c. rhabdoid tumor xenografts compared with control animals. I.v. administration of VSV(DeltaM51) or i.t. injection of MV prolonged the median survival of mice with brain xenografts compared with controls (VSV(DeltaM51): 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(DeltaM51) and MV could be novel effective therapies against human rhabdoid tumor.
Wu
Yushui
Y
Department of Oncology, University of Calgary, the Tom Baker Cancer Centre, and the Clark H. Smith Brain Tumour Research Centre, Calgary, Alberta, Canada.
Lun
Xueqing
X
Zhou
Hongyuan
H
Wang
Limei
L
Sun
Beichen
B
Bell
John C
JC
Barrett
John W
JW
McFadden
Grant
G
Biegel
Jaclyn A
JA
Senger
Donna L
DL
Forsyth
Peter A
PA
D000818:Animals; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009233:Myxoma virus / Q000502:physiology*; D050130:Oncolytic Virotherapy / Q000379:methods*; D018335:Rhabdoid Tumor / Q000628:therapy* / Q000821:virology*; D018116:Vesiculovirus / Q000502:physiology*; D023041:Xenograft Model Antitumor Assays