An artist’s depiction of a brain tumor that can be killed using a virus.
To defeat the deadliest cancer, it’s time to unleash the viruses.
In a small clinical trial of brain cancer patients, a tumor-seeking virus successfully invaded cancer cells and smuggled in molecular detonators, allowing doctors to selectively destroy the deadly growths with a toxic drug. In the 45 study participants, who battled the most aggressive forms of brain cancer known, the virus-drug combination nearly doubled their average survival time while showing no dangerous side effects. The finding, published Wednesday in the journal Science Translational medicinedemonstrates the usefulness of such viruses and also greenlights 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 address this medical need,” they concluded.
Ars has previously reported on cancer-killing viruses, but this new virus works a little differently. Rather than directly killing a cancer cell, the virus lays the groundwork for targeted drug attacks.
The virus, called Toca 511, specifically seeks out and invades cancer cells with broken defense systems that would normally block viral invasion. Once inside, the virus slips the genetic blueprints for an enzyme into the cell’s 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 the chemical bomb: an inactive form of a cancer drug called 5-FU, or 5-fluorouracil. This drug is very effective at killing cancer cells, but it is also highly toxic and generally unsafe to inject directly into patients. With the inactive molecule, administered directly into the brain or intravenously, a tame version can safely roam until it reaches the tumor. There, the lurking CD enzyme transforms it into an active cancer killer.
For the trial, researchers enrolled patients with some of the deadliest forms of recurrent brain cancer, called high-grade gliomas. In a control group that was part of another study of the same types of cancer, patients lived an average of 7.1 months after the first or second recurrence and underwent brain surgery to remove tumor masses. Patients who received Toca 511 and the tame version of 5-FU after brain surgery survived for an average 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 was around brain tumors. This suggests that the virus did indeed enter tumor cells selectively.
Although the results are promising, the study is only a phase I trial and the treatment needs to be tested in larger groups of patients with more controls. The authors report that phase II trials are now underway.
Science Translational Medicine2016. DOI: 10.1126/scitranslmed.aad9784