Cutting-Edge Treatments Provide Hope for Brain Cancer Patients

What was once a dream of the medical community is coming closer to reality.

A brain tumor’s biggest foe could be a virus.

An innovative strategy to treat recurrent high-grade gliomas and glioblastomas, or malignant tumors, using a retrovirus-based gene therapy is being tested in a multicenter clinical trial.

The first phase of the trial determined that a new cancer-fighting treatment created by the company Tocagen was safe for further study. More than 60 clinical sites worldwide are now taking part in the second phase, including NewYork-Presbyterian/Columbia University Medical Center and NewYork-Presbyterian/Weill Cornell Medical Center.

“It’s the combination of gene therapy and pharmacology that makes this trial unique,” says Dr. Adam Sonabend, a NewYork-Presbyterian neurosurgeon and the principal investigator for the trial here.

Dr. Adam Sonabend

First, surgery is performed to remove as much of the tumor as possible. Then, a genetically engineered retrovirus called Toca 511 is injected directly into the brain, in the area where the tumor was removed. The virus delivers a yeast gene, not found in humans, that spreads through cancerous cells and programs those cells to make the enzyme cytosine deaminase (CD). Patients then take an oral medication, Toca FC, which the CD converts into the FDA-approved anti-cancer drug 5-FU. The process selectively kills cancer cells and cells that suppress the immune response against the tumor. Healthy cells are left unharmed.

Although this specific approach to brain tumors is new, using a virus as cancer treatment has been of interest to the medical community for more than a century. One instance occurred in the early 1900s, when a woman’s cervical cancer temporarily regressed after she received a rabies vaccine. But it’s only since the advent of genetic engineering that modern-day scientists have been able to take it further and use a virus’s infectious nature to deliver genes with a therapeutic goal.

A key difference between this study and earlier ones using retroviruses to target cancer is that the Toca 511 laboratory-created retrovirus replicates.

“This is very exciting because, ideally, this will be a self-dosing medication,” says Dr. Sonabend. The theory is that as long as tumor cells are growing within the brain, the virus will similarly multiply to combat them.

Glioblastomas, which are considered the most aggressive and deadly of brain and spinal cord tumors, are not surgically curable and therefore notoriously difficult to treat. Primarily affecting people in their 30s to 60s, they have a recurrence rate of nearly 100 percent, and average life expectancy is 14 months.

If successful, this retrovirus therapy would be a significant advance in treating glioblastomas. Although a third and final trial would need to be completed before treatment could be made widely available, the outlook is promising. The Food and Drug Administration recently granted Toca 511 and Toca FC a Breakthrough Therapy Designation , which means the agency will expedite development and review. The trial data were originally expected to be released in 2018, but in light of the designation, it could be sooner.