Can Scientists Really Harness the Poliovirus to Kill Cancer?

A modified poliovirus created by Duke scientist Matthias Gromeier, MD, has been awared "breakthrough therapy" status from the Food and Drug Administration.
It has shown dramatic sucess in a small number of adults with an aggressive brain cancer.
A trial of the poliovirus for children with brain cancer is scheduled to begin in the near future.
Scientists believe it may kill other cancers, too, but they are proceeding cautiously.
 

by Angela Spivey

Almost 20 years ago, Matthias Gromeier, MD, published the idea that scientists could tame the deadly poliovirus and use it to kill brain tumors. It started with the observation that cancer cells have a receptor that the poliovirus fits into, like a key into a lock.

“There were several of us who saw this at the same time. I was one of them,” Gromeier says.

But Gromeier has been the one to stick with this notion. Some people would consider it outrageous. Inject a virus that can cause a paralyzing disease into someone’s brain? But Gromeier believed he could engineer a way to make the poliovirus harmless—except to cancer cells.

Matthias Gromeier sees many years of work ahead to fully understand the poliovirus immunotherapy he has created.
Your support helps scientists at crucial moments in development of new therapies. To help, visit bit.ly/dcifall

 

He did that, and showed that it worked in mice. Then came many more years of tests in mice and primates, to prove that the modified virus couldn’t cause polio. Finally, in 2012, the Duke researchers were allowed to test the treatment for the first time in humans with glioblastoma, an aggressive brain cancer.

A BREAKTHROUGH?

In May 2016, because of promising early results from those tests, the Food and Drug Administration (FDA) designated the poliovirus as a “breakthrough therapy.”

The breakthrough status means that the FDA sees evidence that the treatment may work better than current treatments for brain cancer. The FDA will give the therapy expedited review and close attention to help ensure its progress. But it’s not a guarantee that the agency will ultimately approve it for general use as a treatment for brain tumors.

“This is a very challenging drug because this is a virus that replicates, infects and kills tumor cells, and that can infect certain immune cells,” Gromeier says. “We know it can work. But we have to find out how we can make it work for everybody.”

LESS IS MORE

In the first human trials, a few patients responded dramatically. Three appear to be cancer free, including Stephanie Lipscomb. She was in college when she received the treatment and is now working as a cancer nurse (see “Survivors” photo essay).

But some other patients, particularly those who received higher doses of the treatment, had debilitating inflammatory reactions. Nancy Justice, a wife and a mother of two sons, was one of

She responded well to the treatment at first, then, after a series of setbacks and improvements, declined and passed away from the brain tumor in April 2016. Patients like Justice taught the researchers that controlling inflammation, by lowering the dose of the treatment and possibly by adding other medications, will be crucial.

“We are still puzzled by the fact that we have the best responses in the patients who got the least amount of virus,” Gromeier says.

The less-is-more effect may happen because the poliovirus works mostly by unleashing the body’s powerful immune defenses.

“I think of cancer as a result of a failing immune system,” says Smita Nair, PhD, a Duke immunologist who is studying the poliovirus. “A tumor has some sort of marker on it—a protein or an antigen—that the immune system can see.” But cancer finds a way to hide. “With the poliovirus,” Nair says, “the idea is that it will kill the cancer cells, and at the same time, it will release the tumor antigen and cause inflammation that will hopefully drive an immune response.”

Nair has begun testing the poliovirus in mice with breast cancer. Just seven days after she injects the poliovirus into the tumor, she sees an increase in immune-system activity.

“I think of cancer as a result of a failing immune system."--Smita Nair

 

Immunologist Smita Nair works closely with Michael Brown, who earned a PhD studying how the poliovirus works to kill cancer.

 

After we administer the poliovirus, we are seeing immune cells—T cells—coming to the tumor,” Nair says. “This is not in one tumor model, but in three models.” These and other early animal studies also suggest that the treatment may kill not only brain tumors, but other types of cancer, too.

TAKING IT SLOW

The possibility of treating other cancers with poliovirus is exciting, but the Duke team is proceeding cautiously. With a $2.5 million grant from the Department of Defense, Nair plans to conduct two to three years of mouse studies. If all goes well, at the end of that time, the team will conduct a pilot tissue study in six women with breast cancer. The women will receive standard of care—chemotherapy plus surgery. Two weeks before surgery, they will get an injection of the poliovirus directly into their tumors. After the tumors are removed, Nair will compare the tissue to a biopsy taken before the poliovirus injection.

Nair will look for changes in immune system cells and in genes linked to inflammation and immune responses. Those findings should help the researchers design the first clinical trials of the poliovirus in women with breast cancer.

Gromeier says, “We have to fully understand how our strategy works before we can move into cancers that occur outside the brain. Moving too fast with clinical trials that are poorly conceived can damage the prospects of a new, promising therapy.”

BEYOND DUKE

Meanwhile, trials in brain cancer patients continue. A new trial at Duke for children with brain tumors is planned and is awaiting final approval. As part of the breakthrough therapy designation, studies for adult brain cancer patients will open at a handful of other cancer centers outside of Duke, though Gromeier can’t say exactly when.

Those multi-center trials will likely combine the poliovirus treatment with chemotherapy, thanks to patients like Brendan Steele. As CBS News program 60 Minutes reported, Steele’s tumor initially grew larger after the poliovirus injection. He was given chemotherapy in hopes of gaining a few more weeks. Soon, his tumor was shrinking. After a second dose of chemotherapy and a few more months, it had disappeared.

Gromeier was excited but puzzled. “Scientifically, no one really knows what’s going on,” he says. “But it’s so attractive because these chemotherapy drugs have been used for decades. We have other patients, not just Mr. Steele, who are responding very well to the combination of the poliovirus with chemotherapy. We are performing laboratory studies combining our virus with traditional chemotherapy to identify the mechanisms at work.” Today, Steele is doing well three years after first receiving the poliovirus.

Matthias Gromeier is a professor of neurosurgery and a professor in medicine and in molecular genetics and microbiology. Smita Nair is an associate professor of surgery and a professor in pathology.