Children’s Minnesota testing vaccine against deadly pediatric brain cancer

Children’s Minnesota is testing the safety of a new vaccine combination to combat one of the deadliest pediatric cancers, which could give new hope for children who would otherwise typically die within months of a diagnosis.

The brain cancer — diffuse midline glioma, or DMG — has confounded clinicians. Because it spreads so rapidly, doctors can’t surgically remove the tumors. The brain’s protective barrier also prevents chemotherapy drugs from killing the cancer cells.

“The cure rate for DMG is less than 1%, and the median overall survival is nine to 11 months,” said Dr. Anne Bendel, the Children’s researcher leading the trial. “And that statistic has not changed since the 1950s.”

University of Minnesota researchers developed a vaccine that stimulates the immune system to attack these cancer cells but discovered in a clinical trial several years ago the cancer cells fight back by releasing proteins that blunt the immune response. The researchers then developed a synthetic peptide that seeks to counteract the cancer response and boost vaccine effectiveness.

Children’s is using the experimental vaccine and peptide in combination with an early stage trial to prove safety and determine the best dosage. Both have been licensed to Minneapolis-based OX2 Therapeutics, a biotech spinoff launched by U of M researchers Michael Olin and Dr. Chris Moertel.

The company is funding the trial and selected Children’s, partly to have a research organization outside the U validate the effectiveness of the combination therapy, Moertel said. Children’s is recruiting patients ages 2 to 25 who either have early stage DMG or a related form of cancer called high-grade gliomas (HGGs). The first patient enrolled two weeks ago.

Gliomas are cancers of the glial cells that protect the spinal cord and neurons, the brain’s thinking cells. Survival is typically around two years for people with this form of cancer, such as the late U.S. Sen. John McCain. Doctors diagnose only about 200 to 300 children with the severe DMG subtype of this cancer each year.

Telling parents of the newly diagnosed that their children have a year or less to live has been awful, said Moertel, a pediatric neurooncologist.

“Our goal is to give these families more time with their children,” he said. “If we can get to the point we have cured them, hip-hip hooray ... but more time translates into all sorts of wonderful things.”

Amanda Bekric of Andover said many trips to Pittsburgh for a different experimental treatment were invaluable, because her daughter, Lejla, lived for two years after her DMG diagnosis.

The child died at age 4 in 2017, but she defied expectations and enjoyed the toddler experiences of walking, talking, attending preschool, picking out clothes and picking occasional fights with siblings.

“My husband called her Sour Patch Kid because she could be super sassy and in your face, and as soon as you gave her attention, she was super sweet and caring and loving,” her mother said.

The family donated her tumor for continued development of brain cancer therapies at multiple U.S. research institutions.

The vaccine in the Children’s trial will go to patients who have already received a diagnosis, which differs from common childhood and seasonal vaccines given widely to people in advance to prevent illness. The principle in both cases is to stimulate the immune system to offer protection, Bendel said.

“If you can give a patient a vaccine that has the proteins that are on the surface of brain tumors, then the immune system will be trained to recognize those proteins as foreign and then attack anything in the body that has those proteins on the surface,” she said.

Moertel and colleagues gave the combination therapy to nine adults with brain cancers in an earlier trial that paved the way for the new pediatric trial.

Median survival was only 11 months, but, for a subgroup of patients, it reached 26 months. If researchers can figure out why that group had better outcomes, Moertel said, it’s possible the vaccine could provide more than just a longer lifespan for terminally ill children.

“If we can break down the tumor’s barrier to allow the immune system to do its job,” he said, “then we are well on the way to helping cure those kids.”

If the experimental peptide proves safe and effective, Olin, Moertel’s colleague at OX2, said he hopes to test its ability to boost treatment of more common conditions, such as breast cancer and melanoma.