Tumor-killing virus nearly doubles survival time of brain cancer patients
To defeat the deadliest of cancers, it's time to unleash the viruses. In a small clinical trial with brain cancer patients, a tumor-seeking virus successfully invaded cancer cells and smuggled in molecular detonators, allowing doctors to selectively blast the deadly growths with a toxic drug.
In the trial’s 45 participants, who were fighting the most aggressive forms of brain cancer known, the virus-drug combo nearly doubled their average survival time while showing no dangerous side effects. The finding, published Wednesday in the journal Science Translational Medicine, demonstrates the utility of such viruses and also provides a green light for the treatment strategy to move on to more trials.
These brain cancers usually have few treatment options and lead to “dismal clinical outcomes,” the authors wrote. However, this new viral therapy has “the potential to fill this medical need,” they concluded.
Ars has reported on cancer-killing viruses before, but this new virus works a little differently. Instead of directly killing a cancer cell, the virus lays the groundwork for targeted drug strikes.
The virus, dubbed Toca 511, specifically seeks out and invades cancer cells with broken defense systems that would normally block the viral invasion. Once inside, the virus slips the genetic blueprints for an enzyme into the cells’ DNA. The cancer cell then unwittingly reads through the blueprints and produces the enzyme, the yeast cytosine deaminase (CD), which acts as a drug detonator.
In the second part of the treatment, doctors send in the chemical bomb: an inactive form of a cancer drug called 5-FU, or 5-fluorouracil. This drug is highly effective at killing cancer cells, but it’s also highly toxic and generally unsafe to inject straight up into patients. With the inactive molecule, delivered either directly into the brain or intravenously, a tame version can safely roam around until it reaches the tumor. There, the CD enzyme lying in wait transforms it into an active cancer killer.
For the trial, researchers enrolled patients with some of the deadliest forms of recurring brain cancer, called high-grade gliomas. In a control group that was part of another study on the same types of cancers, patients lived for a mean of 7.1 months after the first or second recurrence and had brain surgery to remove tumor masses. Patients that received Toca 511 and the tame version of 5-FU after brain surgery survived for a mean of 13.6 months.
Those virus-treated patients had no major side effects from the virus or toxicity from 5-FU. When the researchers scanned the patients' blood after the treatments, they found that the virus was no longer detectable, but it could be found around brain tumors. This suggests that the virus was indeed selectively invading tumor cells.
While the results are promising, the study is only a phase I trial, and the treatment needs to be tested out in bigger groups of patients with more controls. The authors report that phase II trials are now in progress.