Oncolytic Viruses and Cancer Therapy - Page 2

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Nov 29, 2001

Reovirus

Reovirus infections in humans are mild and restricted to the upper respiratory and gastrointestinal tracts, but in general, they are without symptoms. During basic research on the biology of reovirus infection, it was discovered that the Type 3 Dearing strain was capable of replicating in cells with an activated ras signaling pathway, while normal cells were unable to support the infection. It appears that the reovirus utilizes the Ras pathway in a similar manner as the modified herpes simplex virus discussed above. Activated ras oncogene occurs in about 30% of all human cancers, primarily in pancreatic, colorectal, lung and leukemias. Studies with mice have demonstrated that the reovirus is very effective in tumor regression, even with animals with an intact immune system. 2 Clinical trials with humans are sure to follow, given the many attractive features of this natural virus.

Vesicular Stomatitis Virus

Vesicular stomatitis virus is nonpathogenic in humans. This virus has been of interest due to its extreme sensitivity to the antiviral actions of the interferons. Follow-up laboratory work demonstrated that the virus replicated in a majority of cancer cell lines. Balachandran and associates 1 conducted a series of experiments that involved implanting mice with tumors that were defective in p53 function, or transformed with activated myc or ras oncogenes. The virus markedly inhibited the growth of the tumors, while being virtually undetected in normal tissues. Another study indicated that the virus is able to migrate to sites distant from the site of inoculation to inhibit tumor growth. This experiment demonstrated that the virus could be capable of treating metastic cancers, and that an intact immune system of the animals does not have a detrimental effect on the virus’s action. This virus, therefore, holds great promise, as it is harmless to humans, and appears effective against a majority of cancers.

References

1.Balachandran, S., Porosnicu, M. and Barber, G. Oncolytic activity of vesicular stomatitis virus is effective against tumors exhibiting aberrant p53, ras, or myc function and involves the induction of apoptosis. J. Virology Vol. 75, No. 7, pages 3474-3479 (April 2001)

2.Coffey, M., et. al. Reovirus therapy of tumors with activated ras pathway. Science Vol. 282, No. 5392, pages 1332-1334 (Nov. 13, 1998)

3.Norman, K., Farassati, F., and Lee, P. Oncolytic viruses and cancer therapy. Cytokine & growth factor reviews Vol. 12, Issue 2-3,pages 271-282 (June 2001)

4.Norman, K. and Lee, P. Reovirus as a novel oncolytic agent. J. Clin. Invest. Vol. 105, No. 8, pages 1035-1038 (April 2000)

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