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Engineered Virus Inhibits Cancer Metastases

02/04/2013
Diana Gitig, Ph.D.

How efficient have viruses engineered to seek out and destroy cancer cells become?


On this World Cancer Day, Feb 4, 2013, a new option has been added to the arsenal of therapies used to treat HER2+ breast and ovarian cancers: an engineered herpesvirus that not only targets and eradicates HER2+ ovarian and breast tumors in mouse models, but can also halve their metastases to the brain as well.

Transmission electron micrograph of a herpes simplex virus. Credit: Erskine Palmer, CDC




Using viruses to kill cancer cells is appealing; in addition to killing target cells within tumors, viruses can replicate and spread to additional target cells all over the body, potentially reaching metastatic cells. Over the past decade, this approach has become less toxic because researchers have increased the specificity of viruses engineered to target cancer cells.

“The next challenge has been to verify whether such a reprogrammed virus is capable to find and reach the tumor once the virus is administered through a systemic [intravenous or intraperitoneal, not oral] route. This is what has been done in the present work,” said Gabriella Campadelli-Fiume, who runs the Laboratory of Molecular Virology in the Department of Experimental, Diagnostic and Specialty Medicine at the University of Bologna and is an author of a new paper published today in the Public Library of Science Pathogens describing the new virus (1).

To begin, Campadelli-Fiume’s lab transplanted human breast cancer cells overexpressing the protein HER2 into immunodeficient mice to generate a model where breast and ovarian cancers metastasize in a diffuse manner to the peritoneum. Previous research has found that HER2 is overexpressed in many human breast and ovarian cancers and that higher HER2 expression correlates with poorer prognosis. The researchers chose very aggressive, metastatic breast cancer cells that are resistant to transtuzumab, a monoclonal antibody often used to treat HER2+ cancers, to mimic a worst-case scenario.

These mice received an intraperitoneal injection of a herpesvirus genetically engineered to specifically target HER2+ cells. The metastatic burden in treated mice was reduced by about 80% in the ovaries and about 50% in the brain, compared to untreated mice. Metastases to the lungs, however, did not seem to be affected.

“At present, most patients at risk of metastases, after surgery, receive a cocktail of drugs or radiation aimed at preventing metastatic outgrowth,” said Campadelli-Fiume. “These treatments severely impair the quality of life. Even more important, about 40% of patients succumb to malignant (i.e. metastatic) tumors. Therefore we need newer approaches to cancer therapy, in particular as far as metastatic patients are concerned.”

Because the virus reaches and populates tumor masses in the peritoneum, it could be useful for imaging tumors with noninvasive positron emission tomography (PET). In addition, the engineered HER2 herpesvirus can “easily be re-engineered to target different oncoproteins,” said Campadelli-Fiume.

References

1. Nanni, P., V. Gatta, L. Menotti, C. De Giovanni, M. Ianzano, et al. 2013. Preclinical therapy of disseminated HER-2+ ovarian and breast carcinomas with a HER-2-retargeted oncolytic herpesvirus. PLoS Pathog 9: e1003155. doi:10.1371/journal.ppat.1003155