Providence vaccine uses listeria to attack brain cancer

In In The News by Barbara Jacoby

Thumbnail for 5964By: Lynne Terry


On a weekend jaunt with girlfriends, Valerie Miles had just sat down at a long picnic table at a restaurant in San Diego. She picked up the menu and strained to read it but could not make out the words.

The next thing she knew she was in an ambulance. She had had a grand mal seizure. Later, doctors discovered the cause: brain cancer. Miles was only 33 and had four young children, a loving husband and a good job.

The prognosis was not good. Half of those diagnosed with her type of tumor, glioblastoma, the most common brain cancer in adults, do not make it past 14 months. Only 10 percent survive more than five years.

Miles, who lives in Vancouver, was diagnosed in June 2005. She soldiered through treatment and enjoyed a four-year reprieve before the cancer bounced back in 2012, giving her few medical options.

But hope emerged this year when Miles joined a trial of a cancer vaccine. Developed by researchers at the Providence Cancer Center in Portland, the vaccine aims to trigger the body’s immune system to kill the cancer cells.

The vaccine combines brain cancer cells with a virulent bacterium, Listeria monocytogenes. The listeria triggers the kind of immune system response needed to kill the cancer cells.

Immunotherapy has been around for a few decades, and listeria has been used in other cancer vaccines. A phase II trial of a listeria-based vaccine on pancreatic cancer patients extended their lives, researchers announced last year in San Francisco.

But this is the first time a listeria-based vaccine has been developed to attack a brain tumor, Providence researchers said.

“The brain has traditionally been a tough area to target for cancer therapies,” said Keith Bahjat, a key Providence researcher in the project, which was initiated at his lab.

The body has what is known as a blood-brain barrier, which protects the brain from harmful substances but makes it difficult to treat tumors because the barrier blocks most pharmaceuticals from entering the brain. Drugs can be injected directly into the brain, but most patients would object to daily shots in the skull, Bahjat said.

He sees immunotherapy as an effective strategy for targeting brain cancer because the brain is somewhat sequestered from the immune system, which plays a role in determining whether tumors form and how they develop.

Tumors elsewhere in the body have learned how to avoid the immune system but that is not the case with brain. Bahjat suspects that will make them extremely responsive to immunotherapy, once the vaccine jump-starts the immune system.

Using the immune system brings other advantages as well, said Dr. Marka Crittenden, a radiation oncologist and the trial’s principal investigator.

“The immune system has a memory, even of prior infections,” Crittenden said. “If you get the immune system involved, it can destroy the cancer at that time but also work later.”

Providence researchers have worked on the vaccine for three years. Bahjat focused on development, while Crittenden handled regulatory hurdles. A company in Berkeley, Calif., Aduro BioTech, provided the listeria, which has been genetically altered to be far less virulent than usual.

The research included two years of testing on mice. This is the first trial on humans. It will include up to 38 patients who have already undergone surgery, radiation and chemotherapy, the standard treatment.

A Phase I trial, the focus is on dosage. Patients receive an infusion of the vaccine, ADU-623, in an intravenous drip over two hours every 21 days. The dosage will be amped up three times during the year-long trial, with new patients at each level. Researchers will monitor participants closely to determine their physical reaction and immune response.

“Safety is absolutely priority number one,” said Bahjat. “What is the highest dose we can safely give to a patient with a brain tumor? The second priority is characterizing the immune response to our vaccine.”

Miles jumped at the chance to take part. She has a lot to live for, with her children now teenagers and full of dreams of their own. One wants to be a veterinarian. Another a SWAT team member. And a third aims to become an astrophysicist. She wants to see them succeed and enjoy the next phase of motherhood with her husband by her side.

But she is not just thinking about her family.

“This is part of something important that will help maybe not only myself but people in the future,” Miles said.

If the patients do well, a second, then third trial will be launched. Getting the vaccine to market could take five years at least.