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Published on: November 24, 2014
Reovirus as an oncolytic agent against experimental human malignant gliomas
1Departments 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.
Insights
Reovirus effectively targets and destroys malignant glioma cells in laboratory and animal studies. This oncolytic virus shows potent anti-glioma activity, suggesting its potential as a novel cancer therapy.
Area of Science:
- Oncology
- Virology
- Cancer Research
Background:
- Reovirus is a naturally occurring oncolytic virus.
- It replicates in tumor cells by exploiting activated Ras-signaling pathways.
- Ras pathways are frequently activated in malignant gliomas.
Purpose of the Study:
- To evaluate the efficacy of reovirus as an experimental treatment for malignant gliomas.
- To determine reovirus's oncolytic potential against glioma cell lines and patient-derived tumors.
Main Methods:
- In vitro studies using human glioma cell lines.
- In vivo studies involving subcutaneous and intracerebral human glioma xenografts in mice.
- Ex vivo testing on primary glioma cell cultures derived from patient specimens.
Main Results:
- Reovirus demonstrated potent oncolytic activity, killing 83% of tested malignant glioma cell lines.
- Significant tumor regression and prolonged survival were observed in mouse models.
- Reovirus effectively killed 100% of tested primary glioma specimens but not meningiomas.
Conclusions:
- Reovirus exhibits potent anti-glioma activity across in vitro, in vivo, and ex vivo models.
- Oncolysis using reovirus presents a promising therapeutic strategy for malignant gliomas.
- Reovirus holds potential as a treatment for various human cancers.
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