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Reovirus
oncolysis in medulloblastoma is effective in vivo and safe in rodents and
primates
Peter A
Forsyth, Wen Qing Yang, Donna Senger, Huong Muzik, Zhong Q Shi, Penny Brasher,
Richard Dyck
Univ of
Calgary & Tom Baker Cancer Ctr, Calgary, AB, Canada
Introduction.
Medulloblastoma (MB) is a highly
malignant childhood brain tumor.
Reovirus is not known to cause disease in human
adults and usurps activated Ras pathways to produce its dramatic oncolytic
effect.
Since Ras may be activated in MB this could be a promising new treatment
for MB.
In this study we tested 1) the ability of reovirus to infect/kill MB in
vitro & in vivo and 2) safety of intracerebral (IC) injection of reovirus in
nude mice, Fisher rats and 3) cynomolgous monkeys.
Methods/Results.
MB cell lines
(eg. Daoy, TE671, MB from ptc -/+ mice, Daoy+Trk) were infected/killed by
reovirus.
Ras pulldown assays correlated with susceptibility.
TrkC-transfected
MBs (Daoy+Trk)+ NT3 were 50% more susceptible than parental Daoy.
Reovirus
efficacy in vivo was assessed in nude mice with Daoy implanted orthotopically
and 20 days later live (LV;N=8) or dead virus (DV;N=8;control) administered IC.
Mdn survival of LV group (>160 D) was longer than DV group (70 D; p=0.0003).
We next tested reovirus' neuro-toxicity administrated IC using histology (in nude
mice/rats/cynomolgous monkeys) and behavior [using the Morris Water Maze Task
(MWMT)in nude mice/rats].
Monkeys remained well/afebrile, minimal pathological
changes IC and no diffuse encephalitis.
Mice/rats remained well/gained weight
and had MWMT scores equal to controls; rodent histology is pending.
Conclusions.
Oncolytic treatment with reovirus might be an effective treatment for MB.
The
dose/schedule/route of administration should be optimized.
Direct injection of
reovirus IC appears to be safe in two different rodent species and in a primate
(cynomologous monkeys) species.
© Copyright 2002 American
Society of Clinical Oncology
Source:
http://www.asco.org/ac/1,1003,_12-002324-00_18-002002-00_19-00289-00_29-00A-00_42-00ONeill-00_43-00-00_44-00-00_45-00
Author-00_46-00Title-00_47-00Title-00_48-00and-00_49-00and,00.asp?cat=CNS+Tumors&parent=CENTRAL+NERVOUS+SYSTEM+TUMORS
&returnpid=2323
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