How to Help a Virus Kill Cancer

Oncolysis stopped by CCN1 activation

(RxWiki News) Glioblastoma (a form of aggressive brain cancer) has limited treatment options. Recently some studies have tried to make headway in treatment by examining the use of viruses to upload new DNA into the tumor cells, then using a secondary effect to kill the tumor.

Work in this field has been problematic, given the many defenses the human cell has against viral infection.

Researchers are trying to improve the results of the cancer-killing viral therapy by studying how the cells normally defend against a viral infection.

"Ask your oncologist about immunotherapy."

Researchers from Ohio State University Comprehensive Cancer Center looked into increasing the effectiveness of these human-engineered cancer-killing viruses, known as oncolytic viruses. Specifically, the group found that the brain cancer cells signaled others with a protein called CCN1, sounding the alarm to the immune system to begin fighting back.

The protein CCN1 was known to be involved in immune signaling, but testing found that the primary role is to prevent viral infection.

"We found that, in the extracellular matrix, this protein orchestrates a striking cellular antiviral response that reduces viral replication and limits its cytolytic efficacy," said principal investigator Balveen Kaur, who holds a doctorate in molecular biology.

"These findings are significant because they reveal a novel mechanism used by infected cells to fight viral infections and alert adjacent uninfected cells to prepare their defenses to fight off forthcoming viral attacks," Kaur says.

The study found that the protein CCN1 is important in normal immune function, but in this case prevents the viral therapy from working to kill the cancer cells. Normally a good thing, this defense protein usually keeps cells from being infected, but scientists found that it is even more common than usual in these brain cancers, showing up in 68 percent of glioblastoma specimens.

The study builds on Kaur's previous research on CCN1's interactions with cancer cells and oncolytic viruses. Researchers experimented using animal models, planting glioma cells cultivated from human tumors, and injecting oncolytic viruses derived from human herpes virus type 1 (HSV-1).

The research was examining the use of viral infection of cancer cells, but the principals explored in viral infection have broad application in immunotherapy for preventing viral infection as well.

Lowering immune function after intentionally introducing viruses that alter DNA is not without controversy in scientific quarters, but researchers hope to further research in the field of immune therapy in general before beginning to test viral therapy in humans.

Researchers concluded that the protein CCN1 causes a category one immune response, and treatments are currently available to suppress the immune system to enhance the virus' effect on cancer cells. The possible complications and side effects demonstrated in the past few decades with viral therapy may keep this line research purely experimental for some time.

The study was published in a recent issue of the journal Cancer Research.

Full financial disclosure of conflicts of interests and funding was not made publicly available.

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Review Date: 
March 26, 2012