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University of Florida Researchers Unlock New Frontiers in Brain Tumor Treatments

Below is a release from the University of Florida regarding new breakthroughs in brain tumor treatments.

As a physician-scientist and cancer researcher at the University of Florida, Duane Mitchell, M.D., Ph.D., is providing hope for patients in an area where there is often little: treatment for malignant brain tumors. By pioneering several novel brain tumor immunotherapies, which have been translated into first-in-human clinical trials and multicenter phase two studies, Mitchell is advancing some of the most groundbreaking brain tumor treatments in the country.

Throughout the past decade, researchers at the Preston A. Wells Jr. Center for Brain Tumor Therapy at UF Health (which Mitchell co-directs) have discovered, developed, and received FDA approval to advance 12 new investigational therapeutics to treat malignant brain tumors. This has resulted in 13 novel immunotherapy clinical trials that have been launched at UF.

With the help of a UF Health-led collaboration called the ReMission Alliance, researchers have entered a new frontier: combining the best treatment approaches from these trials (which include cancer vaccines, adoptive T-cell therapy, and immune checkpoint inhibitors) to overcome the limitations of a singular approach. This promises to provide new treatment options for more patients, including those who do not respond to traditional immunotherapy.

“UF Health has the largest and most diverse portfolio of immunotherapy trials that were discovered in the lab and advanced to treatment for brain tumor patients of any center in the country right now,” said Mitchell, who is a Phyllis Kottler Friedman Professor in UF’s Lillian S. Wells Department of Neurosurgery, and the associate director for translation and innovation at the UF Health Cancer Center. “Our vision is to establish the National Cancer Institute-designated UF Health Cancer Center as a leading center for advancing combinatorial cancer immunotherapy for brain tumors and pediatric solid cancers, and as a premier destination site for cancer care.”

Primary malignant brain tumors affect about 25,000 people per year in the United States, and these brain tumors are among the most aggressive and difficult to treat. Despite conducting decades of work in the field, researchers have found that the median survival time for glioblastoma – the most common malignant brain tumor in adults – is only about 15 to 18 months. In addition, brain tumors are the most common solid tumors in children and the leading cause of pediatric cancer-related deaths.

At the core of the UF Brain Tumor Immunotherapy Program’s research is the idea that a patient’s own immune system can be weaponized to fight cancer. The basic approach to treatment is to isolate mRNA (the blueprint of the proteins expressed within a cell) from a patient’s own tumor to train the immune system to lead a coordinated attack against cancer cells. A similar approach was used in the development of COVID-19 mRNA vaccines.

The program has expanded an array of next-generation immunotherapy treatments, many of which have shown promise in animal trials and early-stage testing in humans. Some treatments involve personalized adoptive cellular therapy approaches, in which a patient’s own immune cells are activated outside the body in a laboratory and then delivered back to the patient. Another recent development involves a collaboration with engineers to predict the effectiveness of immunotherapy; by using nanoparticles to track cells inside the body, the approach could allow physicians to make real-time adjustments to a patient’s brain tumor treatment.

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UF researchers also recently developed a new algorithm to predict which proteins expressed within brain tumor cells could serve as the best targets to stimulate a potent anti-tumor response, allowing the development of a precision immunotherapy approach that is tailored to each patient.

The Preston A. Wells Jr. Center for Brain Tumor Therapy is part of the Lillian S. Wells Department of Neurosurgery at UF, which ranks fourth nationally in National Institutes of Health funding. Since 2016, the center has more than doubled its staff to include 115 individuals, from dedicated physicians and researchers to faculty and staff members. And research expenditures total more than $11 million per year.

“We’ve grown because these novel therapeutics have made us a destination center for brain tumor treatment in the United States, with patients traveling to UF Health from 46 of the 50 states,” said Mitchell, who also serves as UF assistant vice president for research, associate dean for clinical and translational sciences at the UF College of Medicine and director of the UF Clinical Translational Science Institute.

UF’s multidisciplinary approach to solving the problem of cancer has been key to the Brain Tumor Immunotherapy Program’s success, as has critical infrastructure. A specialized manufacturing facility on campus allows for the translation of cancer research discoveries from the lab to the clinic. The lab can generate clinical-grade biologic products that meet FDA specifications for therapies to be delivered to patients on clinical trials, leading to significant savings in the time and cost to manufacture new drugs.

“We are extremely proud of bringing together cancer immunologists, neurosurgeons, neurologists, and medical and pediatric oncologists to attack one of the most devastating cancers known,” said Jonathan D. Licht, M.D., director of the UF Health Cancer Center. “The Brain Tumor Immunotherapy Program at UF is one of our signature achievements, and we are very proud of the continued progress it is making.”

Now, UF researchers are reaching even greater heights as they advance their treatment platforms from personalized immunotherapy to precision immunotherapy. Personalized immunotherapy involves taking the patient’s own tumor-derived RNA and making a personalized vaccine or T-cell therapy. Precision immunotherapy goes a step further in individualizing treatment by identifying which altered proteins expressed within the tumor cells are meaningful to the unique immune system of each individual patient. This allows for a bespoke immune treatment, tailored to the individual’s tumor profile and immune system genetic makeup.

“Because of the vast computing power and resources in artificial intelligence and data science at UF, we can use algorithms and data to predict how a patient’s immune system is likely to respond, and design (in real time) an immunotherapy specifically targeted against the brain tumor,” Mitchell said. “This individualized approach should allow us to unlock a much more specific, durable, and comprehensive immune response, hopefully giving many more patients a shot at a cure.”

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