Establishing and Credentialing a PLGA Xenograft Collection
Award: $375,000 over 3 years (awarded 2023)
Principal Investigator: David H. Gutmann, MD, PhD, Washington University School of Medicine
Pediatric low-grade gliomas (pLGGs) are the most common brain tumors in children. While these tumors are often slow-growing, they can cause lifelong neurological disability, including vision loss, seizures, balance problems, and cognitive impairment. Despite their prevalence, progress toward safer, more effective treatments has been limited, largely because researchers lack reliable preclinical models that accurately reflect these tumors and allow meaningful drug testing.
Most pediatric low-grade gliomas fail to grow in traditional laboratory systems, and existing animal models do not faithfully replicate the biology, genetics, or behavior of tumors seen in children. Without validated models, promising therapies cannot be rigorously tested before reaching patients, creating a major bottleneck in treatment development.
This project addresses that challenge by establishing a credentialed repository of pediatric low-grade glioma patient-derived xenografts (PDXs), tumors grown in mice directly from a child’s tumor tissue. These models preserve the molecular, cellular, and architectural features of the original tumors and can be used for biologically relevant drug testing, biomarker discovery, and translational research. By building this shared infrastructure, the project lays the foundation for accelerating therapeutic discovery while reducing unnecessary risk to children.
With support from the Pediatric Brain Tumor Foundation, this project has achieved substantial, measurable progress toward its original goals within its first two years, demonstrating both scientific rigor and strong return on philanthropic investment.
To date, the Gutmann Laboratory has successfully generated primary pLGG cell lines from 10 children, capturing the most common and clinically relevant molecular drivers of disease, including KIAA1549:BRAF fusions, BRAFV600E mutations, and NF1 loss. Each of these models exhibits the critical biological properties required for reliable downstream analysis, establishing a strong foundation for translational research.
Importantly, several of these patient-derived cell lines have now been successfully transplanted into the brains of immunocompromised mice to generate authentic pLGG PDXs. Rigorous pathologic review confirms that these xenografts faithfully mirror the architecture, growth behavior, and molecular features of the original patient tumors validating this approach as a dependable and clinically relevant modeling platform.
Beyond model creation, this growing pLGG collection is already powering new discovery. These validated models are actively being shared with leading pediatric neuro-oncology researchers across the country, extending the impact of this investment far beyond a single institution and strengthening the national research infrastructure required to accelerate progress for children with brain tumors.
Together, this progress demonstrates that the project has successfully advanced from proof-of-concept to a validated, functional research infrastructure, one that is now actively enabling translational science and bringing the field closer to safer, more effective treatments for children living with pLGGs.
