UF researchers to test novel treatments for medulloblastoma

By Michelle Jaffee

University of Florida researchers have received approval from the Food and Drug Administration to test two new experimental therapies in first-ever human clinical trials for a subtype of medulloblastoma, the most common pediatric malignant brain tumor.

The two Phase I trials to treat Group 4 medulloblastoma, expected to begin this fall and next spring, will separately be led by Duane Mitchell, M.D., Ph.D., and Elias Sayour, M.D., Ph.D., investigators with UF’s McKnight Brain Institute and the UF Health Cancer Center.

Doctors Duane Mitchell and Elias Sayour
(From left) Drs. Duane Mitchell and Elias Sayour

Mitchell’s trial will test combining two distinct techniques: precision adoptive T-cell therapy and immune checkpoint blockade with PD-1 inhibitors. Adoptive T-cell therapy, developed at UF, has been shown to be safe and feasible for children with medulloblastoma in previous trials, Mitchell said, while PD-1 inhibitors are FDA-approved to treat some other types of cancer. The new trial will involve using mRNA expressed from a patient’s own Group 4 medulloblastoma tumor to stimulate T-cell responses directed at the cancer.

“This will be for children with a relapse of Group 4 medulloblastoma,” said Mitchell, director of the UF Clinical and Translational Science Institute and co-director of UF’s Preston A. Wells Jr. Center for Brain Tumor Therapy. “The initial study is a pilot to confirm safety and feasibility in six patients, and then we anticipate expanding the trial.”

Sayour pointing at a brain tumor on a scan

Sayour’s trial will use an mRNA cancer vaccine developed by his lab to reprogram the immune system to attack the cancer. It is the same technique he is currently testing in a Phase 1 pediatric clinical trial for glioblastoma, the most aggressive and lethal brain tumor.

Glioblastomas tend to form in the frontal lobe or temporal lobe of the brain, while medulloblastomas develop in the cerebellum, at the back of the brain.

The five-year survival rate for medulloblastoma is about 80%, according to the National Cancer Institute, but prognosis can be affected by multiple factors, including the stage of the cancer, how the patient responds to treatment and their age and health when diagnosed.

“Recurrent medulloblastoma in every form is fatal,” said Sayour, co-leader of the Immuno-Oncology and Microbiome research program at the UF Health Cancer Center. “We are in this to provide hope that we can move the needle.”

“The ultimate goal is we want to cure kids with brain cancers and see immunotherapy treatments move into frontline treatments to perhaps avoid or diminish some of the toxicities of standard treatments we use now,” said Mitchell, associate director for translation and innovation at the UF Health Cancer Center.

The trials will be the 14th time over 10 years that UF has brought novel therapeutic approaches for malignant brain tumors from preclinical studies to human clinical trials, he said.

Researcher examines liquid

The two new trials will be supported by the Medulloblastoma Initiative, an organization that works in partnership with Children’s National Hospital in Washington, D.C. In 2021, the Medulloblastoma Initiative established the Cure Group Four Consortium to support a series of planned clinical trials.

Children’s National is a member of the UF-led ReMission Alliance Against Brain Tumors, a network of experts from top peer institutions and vested collaborators affected by brain cancer. 

Additional clinical-research infrastructure support for the new trials comes from the McKnight Brain Institute, the UF Health Cancer Center, the Lillian S. Wells Foundation and under a broader $12 million gift from The Harris Rosen Foundation to advance innovative brain tumor immunotherapy research and care at UF Health and support the ReMission Alliance.