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UF Health researchers use immunotherapy to treat malignant brain tumors

When pediatric patients with brain cancer receive conventional treatment for their disease, they often are given an infusion of stem cells that create blood cells to replace those obliterated by chemotherapy.

UF Health researchers have found that this infusion combined with immune cells “educated” with the genetic material of the individual’s tumor can help treat brain tumors in mice, according to a study published recently in the journal OncoImmunology.

In melanoma, a cancer of the skin, blood constantly flows through the tumor. This allows the immune system to learn the tumor and produce antigens, material that triggers the immune system to attack the tumor. But brain tumors produce few identifiable antigens, said UF Health researcher Catherine Flores, Ph.D., the study’s lead author. That’s partly because the blood-brain barrier that protects the brain from pathogens and other diseases that might attack it also keeps brain tumors from being exposed to the immune system.

“Part of the success of treating melanoma with adoptive cellular therapy may be because of the fact that melanoma is exposed to your immune system more than your brain,” said Flores, an assistant professor in the department of neurosurgery and principal investigator of the hematopoietic stem cell engineering laboratory within the Preston A. Wells Jr. Center for Brain Tumor Therapy and the UF Brain Tumor Immunotherapy Program. “Your body doesn’t naturally like to have strong inflammatory responses in your brain, so we think this may allow brain tumors to be immunologically silent.”

Working in mice afflicted with glioblastoma, researchers used genetic material from the mice’s tumors to “educate” their immune cells to recognize and attack the brain tumors. The researchers found that using this method, called adoptive cellular therapy, together with an infusion of hematopoietic stem cells — which create disease-fighting white blood cells — boosts the immune system’s ability to fight off glioblastoma in the mice.

The researchers saw that in addition to migrating to the bone marrow to become factories to produce more tumor-fighting immune cells, the stem cells encouraged “educated” immune cells to migrate to the tumors within mice’s brains and more efficiently kill invasive tumor cells.

“They migrated very specifically to areas of tumor growth and actually coordinated recruitment of additional immune cells to the site of brain tumor growth,” said Duane Mitchell, M.D., Ph.D., a co-author of the paper and director of the UF Brain Tumor Immunotherapy Program. “This is a new discovery within our lab group which really has a lot of potential to alter the way we think about delivering cellular adoptive therapy and the use of stem cells.”

Currently, Mitchell’s group is conducting a phase II clinical trial along with other institutions using this kind of therapy in children with recurrent brain tumors. Mitchell said they hope to develop more clinical trials to try the approach in other pediatric patients. Children who have glioblastoma are given chemotherapy that wipes out their immune system, which gives the infusion of hematopoietic stem cells more of a chance to target their brain tumors.

The researchers also hope this same method will translate to other types of cancer.

“We like to think of this as a platform technology approach. If these approaches are effective, we can make them more broadly applicable and they can ultimately be translated into therapies for other cancers and diseases,” Mitchell said. “That way, these approaches are more attractive for commercial development and there’s even more opportunity for larger numbers of patients to benefit.”

Flores recently received an $87,500 grant from The Florida Center For Brain Tumor Research and Accelerate Brain Cancer Cure to study this approach.

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