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Reovirus
as an oncolytic agent against experimental human malignant gliomas
Wilcox
ME, Yang W, Senger D, Rewcastle NB, Morris DG, Brasher PM, Shi ZQ, Johnston RN,
Nishikawa S, Lee PW, Forsyth PA
Departments
of Oncology and Clinical Neurosciences, University of Calgary, and Tom Baker
Cancer Centre, Alberta, Canada
Background.
Reovirus is a naturally occurring oncolytic virus that usurps activated
Ras-signaling pathways of tumor cells for its replication.
Ras pathways are activated in most malignant gliomas via upstream signaling by
receptor tyrosine kinases.
The purpose of this study was to determine the effectiveness of reovirus as an
experimental treatment for malignant gliomas.
Methods.
We investigated whether reovirus would infect and lyse human glioma cell lines
in vitro.
We also tested the effect of injecting live reovirus in vivo on human gliomas
grown subcutaneously or orthotopically (i.e., intracerebrally) in mice.
Finally, reovirus was tested ex vivo against low-passage cell lines derived from
human glioma specimens.
All P values were two-sided.
Results.
Reovirus killed 20 (83%) of 24 established malignant glioma cell lines tested.
It caused a dramatic and often complete tumor regression in vivo in two
subcutaneous (P =.0002 for both U251N and U87) and in two intracerebral (P
=.0004 for U251N and P =.0009 for U87) human malignant glioma mouse models.
As expected, serious toxic effects were found in these severely
immunocompromised hosts.
In a less immunocompromised mouse model, a single intratumoral inoculation of
live reovirus led to a dramatic prolongation of survival (compared with control
mice treated with dead virus; log-rank test, P<.0001 for both U251N and U87
cell lines).
The animals treated with live virus also appeared to be healthier and gained
body weight (P =.0001).
We then tested the ability of reovirus to infect and kill primary cultures of
brain tumors removed from patients and found that it killed nine (100%) of nine
glioma specimens but none of the cultured meningiomas.
Conclusions.
Reovirus has potent activity against human malignant gliomas in vitro, in vivo,
and ex vivo.
Oncolysis with reovirus may be a potentially useful treatment for a broad range
of human cancers.
PMID: 11416111 [PubMed - indexed for MEDLINE]
Source:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11416111&dopt=Abstract
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