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Fall 2015 : The cold virus versus cancer

Unleashing the cold virus to kill cancer

MD Anderson researchers are turning the common cold virus into a cancer-seeking missile that attacks brain tumors

BY Ronda Wendler

Phil Baumann prepares to take a spin in the 1967 Ford Mustang he bought and restored in high school. Baumann, who owns a successful paint and body shop, is battling brain cancer. Photo: Wyatt McSpadden

Medically speaking, Phil Baumann shouldn’t be alive.
Four years ago, at age 47, he was diagnosed with a fast-growing and incurable form of brain cancer called glioblastoma.

I’d been having some pretty bad headaches,” says Baumann, now 51. “Then one night, I had the worst headache of my life.”

The pain convinced the usually stoic paint-and-body shop owner to seek care at a freestanding emergency center, where doctors ordered a CT scan.

Phil’s wife, Misty, remembers what happened next “like it was yesterday.”

“The doctor showed us Phil’s scan. It revealed a tangerine-sized mass on the right side of his brain.”

Baumann sought treatment at MD Anderson where surgeons removed the tumor and doctors prescribed aggressive radiation and chemotherapy. As predicted, in six months the tumor came roaring back.

“You can’t escape glioblastoma,” Baumann says. “My doctors warned me it would return, and it did. It’s scary stuff.”

‘Grow and Go’

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.

“My doctor told me a glioblastoma is like a weed that keeps sprouting runners or tendrils,” Baumann says.

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. Baumann was faced with those dismal odds and worried he’d become one of the 12,000 Americans who die from the disease each year. The brain cancer has been named a target of the Moon Shots Program (see "Moon shots mission escalates to confront six more cancer types").

Worry turned to hope when he was offered the opportunity to enroll in an
MD Anderson clinical trial that uses the common cold virus to battle glioblastoma.

“This was my last chance, so I jumped at it,” he says. “It’s an aggressive tumor, so I wanted an aggressive therapy.”

Husband-and-wife researchers Candelaria Gomez-Manzano and Juan Fueyo found a way to turn the virus that causes the common cold into a cancer-seeking missile. They named it Delta 24. Photo: Wyatt McSpadden

Cancer-seeking missile

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.

Neurosurgeon Frederick Lang helped take Delta 24 from the lab to the operating room. Photo: Adolfo Chavez III

Outwitting cancer

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.”

Unchartered territory

Six weeks after Baumann was injected with Delta 24 — and against all odds — his brain scan showed his tumor stopped growing. Eventually the tumor vanished and Baumann remained cancer free for four years — until this fall when the tumor reappeared.

Doctors are discussing the next steps for Baumann, who Lang says has made history by living cancer free longer than any other participant in the trial.

“I’m extremely blessed that I’ve been given extra time to be a husband to Misty and a father to our 12-year-old son, Colby,” Baumann says.

Like Baumann, two of the other 25 patients enrolled in the trial to test Delta 24’s effectiveness also saw their tumors vanish, though both 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.”

But the most intriguing challenge, Lang says, is to pinpoint what’s unique about the immune systems of Baumann and the other two patients whose tumors disappeared after the virus was injected.

“Can we make patients who didn’t respond look like the three who did? This is what we’ll be working on.”

Phil Baumann, his wife, Misty, and their son, Colby, started CureFest to raise money for brain cancer research. Photo: Wyatt McSpadden

PAYING HOPE FORWARD

To raise money for brain cancer research at MD Anderson, Phil and Misty Baumann, with help from family and friends, host an annual nonprofit event known as CureFest.

Held each spring at the Humble Civic Center, CureFest features a dozen live bands performing on two stages, a classic car exhibition, more than 75 vendor booths offering community services, retail items and handcrafted goods, and a live and silent auction. Favorite auction items in the past have included autographed memorabilia from NFL players such as Troy Aikman, exotic fishing trips, Texans tickets, and even a tricked-out golf cart custom-painted by Phil Baumann.

Children’s activities include an inflatable moonwalk, face painting, an obstacle course, rock wall climbing and more.

Recently, the Baumanns expanded CureFest by adding fundraising golf and tennis tournaments, held separately throughout the year.

“Friends have asked, ‘What can we do, what do you need?’” says Phil Baumann. “All I ask now is that you help us pay the hope forward to help other families in need of a cure.”

Since launching in 2012, CureFest has raised more than $500,000 for brain cancer research at MD Anderson.