Glioblastomas, or malignant gliomas, are sometimes called “grow-and-go” tumors. They make their own blood supply, which fuels the tumors’ rapid growth and helps them hatch satellite tumors. Each tumor sends out tentacles that infiltrate and dig deep into normal brain tissue.
Without treatment, a glioblastoma tumor doubles in size every two to three weeks.
Neurosurgeons may seemingly remove the entire tumor, but hidden cancer cells remain seeded in the brain and, inevitably, the tumor comes back.
When glioblastoma returns, time is short. Even with treatment, survival time following diagnosis is 14 months — 12,000 Americans die from the disease each year. The brain cancer recently was named a target of the Moon Shots Program.
Confronting this very aggressive cancer takes a creative approach such as an MD Anderson clinical trial that’s using the common cold virus to battle glioblastoma.
The experimental therapy is the brainchild of husband-and-wife researchers Juan Fueyo, M.D., and Candelaria Gomez-Manzano, M.D., who have been laboring over what they call their “big idea” for 15 years.
Working in a secured laboratory at MD Anderson, they found a way to genetically modify the adenovirus that causes the common cold, transforming it instead into a cancer-seeking missile that attacks brain tumors.
“We could have experimented with any virus,” Fueyo says, “but we chose the cold virus because it doesn’t need to be re-engineered much to make it safe for patients, yet it’s effective against cancer.”
The altered virus is injected through a hole in the skull, directly into the patient’s tumor. It’s the first time the cold virus has been used in this way.
Some called the couple medical explorers. Others called them crazy.
“At first, everybody had doubts,” says Fueyo, research director in MD Anderson’s Brain Tumor Program. “They didn’t understand the concept and they thought it was dangerous. We’re talking about a live virus, injected into patients in enormous doses.”
Gomez-Manzano remembers being unable to sleep the night the first patient was injected.
“I was so apprehensive,” she recalls, “and very relieved to learn the next morning that the patient suffered zero side effects.”
Fueyo and Gomez-Manzano named their virus Delta 24 — a moniker shared with a type of submarine that seeks out targets and blasts them with ballistic missiles.
“Our virus behaves similarly,” Fueyo says. “It’s engineered to be safe for cancer patients by targeting proteins that exist only in cancer cells, while leaving healthy tissue alone.”
When the virus detects a cancer cell, it enters the cell and begins making copies of itself nonstop. The malignant cell fills with viral particles, then explodes. With each explosion, the Delta 24 viral particles burst forth and move forward in a wave-like motion to infect other cancer cells. This continues until all tumor cells have burst.
If a patient’s cancer comes back, as glioblastoma almost always does, Delta 24 continues to recognize and attack it.
“We’re almost creating a vaccine inside the brain, specifically against the tumor,” says Frederick Lang, M.D., a professor of Neurosurgery at MD Anderson who helped move the therapy beyond the lab and into clinical trials for patients.
Virus-based cancer treatments, sometimes referred to as “virotherapy,” are generating a tremendous amount of excitement in the oncology world, says Lang, who also is director of clinical research in MD Anderson’s Neurosurgery department.
“All human cancers develop a protective shield that makes them invisible to the immune system,” Lang explains. “Viruses deactivate this shield in a very sneaky way.”
By infecting a tumor with the Delta 24 cold virus, the immune system is tricked into thinking, “there’s a common cold here, let’s go kill it.” Immune cells rush to the tumor and unleash an all-out attack against the cold virus. The tumor, caught up in this “war,” becomes “collateral damage” as it is destroyed in the same attack.
Delta 24, working with the immune system, delivers a one-two punch to knock out cancer cells.
“Cancer can be wily because it does everything possible to dodge destruction,” Lang says. “But viruses are equally tricky in their mission to invade cells and propagate.”
Three of the 25 patients enrolled in the trial to test Delta 24’s effectiveness saw their tumors vanish, though two relapsed, and one has died.
Half the remaining patients experienced what doctors call a “partial response.” Their tumors shrank but didn’t disappear, and they lived longer than expected. The other half simply didn’t respond to the virus. Overall, the trial’s results are medically significant, says Lang. “To have these kinds of results in an early-stage trial — where half of patients exceeded life expectancy, and three saw their tumors vanish — is beyond all expectations.
Lang shared the trial’s initial results at the Society for Neuro-Oncology’s annual meeting this past November, where he said we’ve reached “a turning point in cancer care.”
To bring the therapy to more patients faster, and to make it even more effective, the Delta 24 virus is now being tested in combination with other drugs at several sites throughout the world. Studies testing new ways to deliver the virus are also in the works, Lang says.
One will use a new type of catheter that prevents Delta 24 from leaking out of the tumor — a problem of the current procedure — while another will use stem cells to deliver the virus.
“We’ll load Delta 24 into stem cells, inject those stem cells through a puncture in the groin, and then those loaded stem cells will snake their way upward through the network of veins and arteries until they home in on the tumor,” Lang explains. “Instead of injecting the tumor in just one spot, we’re painting the entire tumor with a cancer-fighting virus.”
Read more about this approach and a patient who has benefited from it in MD Anderson's Conquest magazine.