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Pharmaceuticals

Virus helps unmask anticancer drug to attack brain tumors

Phase I clinical trial results show promise for new glioma treatment

by Michael Torrice
June 6, 2016 | APPEARED IN VOLUME 94, ISSUE 23

For patients with extremely aggressive brain tumors called high-grade gliomas, treatment options are limited, especially for recurring forms of the disease.

But results from a Phase I clinical trial show promise for a treatment that combines a virus and a prodrug (Sci. Transl. Med. 2016, DOI: 10.1126/scitranslmed.aad9784).

Gliomas exist in two forms in the brain— as a solid tumor and as tumor cells that infiltrate healthy tissue. Neurosurgeons can remove the solid tumor, but not the infiltrate. So after surgery, patients receive both radiation and chemotherapy to attack this remaining diffuse tumor tissue.

Unfortunately, anticancer drugs struggle to reach this tissue because they have a hard time passing through the blood-brain barrier. The new treatment, developed by the biopharmaceutical company Tocagen, acts like a Trojan horse to produce an anticancer drug in glioma tissue, says Michael A. Vogelbaum of the Cleveland Clinic Foundation, who led the trial.

During testing, neurosurgeons injected an engineered virus called Toca 511 into patients’ brains. The virus infects tumor cells and delivers a gene that makes the cells produce an enzyme called cytosine deaminase, which converts 5-fluorocytosine, a prodrug patients took as a pill, to 5-fluorouracil, an anticancer drug. Though 5-fluorocytosine can effectively pass the blood-brain barrier, 5-fluorouracil cannot.

In the trial, which involved 45 patients, the scientists confirmed that the virus spread through patients’ tumor tissue and successfully delivered the enzyme gene. These patients survived on average almost twice as long as those in another study receiving standard glioma treatments.

Vogelbaum says a Phase II/III trial of the treatment is already under way.

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Comments
Shiva guduru (June 6, 2016 8:26 PM)
This is an excellent strategy...So many small molecules are not cross from BBB and unable to serve as drugs..
Louis Descamps (June 24, 2016 3:29 PM)
There's obviously a reason for this, but can someone explain why the virus is injected in the brain rather than the drug itself?

It confuses me, as a brain injection is still needed.

Thanks in advance.

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