Duane Mitchell
University of Florida, FL·Medicine & Clinical Research
Brain tumors in children remain among the hardest cancers to treat, and even promising laboratory discoveries often stall before reaching patients. Two efforts here address both ends of that gap: one develops a personalized immune therapy for aggressive pediatric brain tumors, and the other builds the statewide infrastructure that helps scientific findings move into clinical care and communities.
- Fields
Medicine & Clinical Research
Microbiology & Immunology
Public Health & Epidemiology
- Topics
pediatric high-grade glioma
medulloblastoma
brain stem glioma
- Grants
- 2 known grants, through Jun 2032
What they work on
- Evaluate the safety, efficacy and immune effects of adoptive T cell therapy targeting neoantigens and uniquely expressed tumor-associated antigens in preclinical models of pediatric high-grade glioma.
- Determine whether antigen-specific memory T cells can be selectively isolated and expanded in the laboratory from pediatric high-grade glioma patients who previously received adoptive cellular therapy.
- Conduct a phase 1 clinical trial of precision adoptive cellular therapy, using tumor-specific RNA-pulsed dendritic cells and the SELEX-CTL expansion platform, in children, adolescents and young adults with invasive high-grade glioma.
- Advance the science of translation by developing innovations in clinical trial design and artificial intelligence and digital health solutions to overcome persistent barriers in clinical and translational research.
- Build a scalable learning health community across Florida, using the OneFlorida+ Clinical Research Network and Data Trust and county extension reach to engage rural and urban populations and sustain translational advances.
More about the research
The brain tumor project builds on an adoptive cellular therapy platform, in which a patient's own T cells are expanded outside the body and given back. In the earlier version, dendritic cells, the immune system's instructors, were loaded with total RNA from a patient's tumor and used to expand many different tumor-reactive T cells. The team reports safety and feasibility along with encouraging preclinical and early clinical results in first-in-human phase I/II trials in medulloblastoma, high-grade glioma, and brain stem glioma, including some patients with prolonged disease-free remission of two to five years. A central difficulty is that tumors are not uniform: different cells carry different targets, and patients differ from one another. The next-generation approach combines three pieces: a cancer immunogenomics algorithm developed in the lab to profile each patient's tumor antigens, a gene enrichment strategy that lets hundreds of tumor-specific targets be represented in a single pool of tumor-specific RNA, and SELEX-CTL, a platform for selectively expanding tumor-reactive killer T cells that start at only one to three percent of cells after stimulation. Plans include testing this therapy in preclinical models of pediatric high-grade glioma against both neoantigens and tumor-associated antigens, isolating and expanding antigen-specific memory T cells from treated patients, and running a phase 1 clinical trial in children, adolescents and young adults with invasive high-grade glioma.
Why it matters
Children with high-grade glioma still face poor outcomes despite surgery, radiation and chemotherapy, so a personalized T cell therapy that can hit hundreds of patient-specific tumor targets at once could offer a new option and is intended to progress to an early-phase clinical trial. The translational science hub aims to bring research opportunities and evidence-based care to rural and urban communities across northern and central Florida, improving how quickly discoveries reach patients.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Daniel Rader
University of Pennsylvania, PA·Genetics
Build and refine a prioritized list of liver-expressed genes at genomic loci associated with both plasma lipid traits and at least one cardiovascular disease, by systematically ingesting and analyzing large-scale genome-wide association and sequencing data.
Frederick Moeller
Virginia Commonwealth University, VA·Medicine & Clinical Research
Strengthen translational research workforce training across the partner institutions so that researchers can recruit a broad range of patient populations into clinical studies.
Nazanin Majd
University of Texas MD Anderson Cancer Center, TX·Medicine & Clinical Research
Run a phase II clinical trial of the checkpoint inhibitors nivolumab and ipilimumab in patients with Shh medulloblastoma, and test whether clinical outcomes correlate with U1 (r.3A>G) snRNA mutation status.
The school
University of Florida: 65 labs on PI Pages, $1.3B a year on research, 795 research doctorates a year.
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