Cancer Viral Therapy Backfires

Glioblastoma viral therapy fails because immune system attacks viruses

(RxWiki News) A novel method of treating aggressive brain tumors uses viruses that kill the cancer cells. While safe, a recent study finds the therapy isn’t as effective as hoped.

The body’s own immune system attacks anticancer viruses being used to treat a fast-growing brain cancer. The body sees these viruses as invaders – like infections – and works to eliminate them, a new study found.

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Researchers at the Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC – James) conducted the study which uncovered this phenomenon.

The aggressive brain tumor investigators were studying is called glioblastoma. Most people live about a year with the diagnosis.

Keith L. Black, MD, chair and professor of Cedars-Sinai’s Department of Neurosurgery, told dailyRx News, “In this paper, the authors demonstrate that some of the immune cells recruited by the anticancer viruses to kill brain cancer cells are also killing the virus. This means that the treatment, if it were to be used in patients, would need to be even more complicated because one would be required to effectively block the patients’ immune cells from killing the viruses used for treatment.”

Dr. Black is director of the Cochran Brain Tumor Center, director of the Maxine Dunitz Neurosurgical Institute and the Ruth and Lawrence Harvey Chair in Neuroscience at Cedars-Sinai.

The study found that the body responds to the viruses with natural killer (NK) cells. The NK cells go after viruses that have specific molecules on their surface called receptors. These receptors are known as NKp30 and NKp46.

"These receptor molecules enable the NK cells to recognize and destroy the anticancer viruses before the viruses can destroy the tumor," a senior author Michael A. Caligiuri, MD, director of OSUCCC-James, said in a press release.

For this study, the scientists used what’s known as a noncolytic herpes simplex virus, human glioblastoma tumor tissue and mouse models.

"To understand this process, we went back to the laboratory and showed that NK cells rapidly infiltrate tumors in mice that have been treated with the therapeutic virus,” said Dr. E. Antonio Chiocca, who was professor and chair of neurological surgery while at Ohio State University.

“These NK cells also signal other inflammatory cells to come in and destroy the cancer-killing virus in the tumor."

Dr. Black, who was not involved in the study, says the viral therapy probably failed for a number of reasons, including the extreme difficulty of delivering a virus throughout the brain.

“Most of these viruses can only travel a few millimeters within the brain. The cancer cells are throughout the brain, and even if the virus were effective in killing cancer cells in a very localized region, the cancer cells beyond the reach of the virus would continue to grow and ultimately result in failure of the treatment,” Dr. Black told dailyRx News.

The findings from this study were published November 25 in the journal Nature Medicine.

Funding for this study came from the US National Institutes of Health, the National Center for Research Resources, an American Medical Association Foundation Seed Grant, the Dardinger Neuro-oncology Laboratory and Pelotonia.

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Review Date: 
December 1, 2012