A research team from the University of Cincinnati Cancer Center has been awarded a $40,000 grant from Ride Cincinnati to study a new approach for treating glioblastoma, an aggressive form of brain cancer. The project focuses on developing a delayed release wafer containing an immunostimulatory molecule designed to activate the central nervous system's immune response after surgical removal of the tumor.
Jonathan Forbes, MD, principal investigator and associate professor in UC's Department of Neurosurgery, highlighted the challenges in treating glioblastoma. He explained that the blood-brain barrier prevents many medications from reaching tumor cells and that the brain’s immune environment is typically unresponsive to cancer. "After surgery to remove the tumor, we have unencumbered access to a resection cavity that we know microscopically is invaded by tumor cells," Forbes said. "Why not use this access to enhance the central nervous system's ability to clear residual tumor cells?"
Medical student Beatrice Zucca described how the team selected Interleukin-15 (IL-15) as their chosen molecule. "IL-15 is exceptionally effective at activating immune populations that are critical for recognizing and killing cancer cells," Zucca said. "It improves their survival, expands their numbers and enhances their cell-killing function, making it an ideal candidate for driving a coordinated immune attack against a highly-resistant cancer like glioblastoma."
The researchers will test their preparation using glioblastoma-on-a-chip technology developed with Ricardo Barrile, PhD, assistant professor of biomedical engineering at UC. Barrile explained: "An organ-on-a-chip is a miniaturized model of a living organ engineered to incorporate the minimal biological elements needed to recreate specific disease conditions." His lab created a model combining human brain and glioblastoma cells using 3D printing techniques and included channels mimicking blood vessels and immune responses.
"This provides a 'human-relevant' platform to test therapies safely and accurately before they reach a patient," Barrile said. "Integrating the immune system was the missing piece and is the key to capture the natural composition of glioblastoma, which in a patient is typically made up to 30% of immune cells. These cells are typically lost during in vitro cell culture."
Barrile also noted potential future applications: "We are building a platform that could eventually predict a specific patient's response to immunotherapy. By using a patient's own cells on our chip, we can identify the best therapeutic approach for that specific individual before treatment even begins," he said. "We are essentially moving from a one-size-fits-all approach to a tailored-to-you strategy."
Forbes added that other research at UC aims to overcome drug delivery challenges by temporarily opening the blood-brain barrier with focused ultrasound technology. "It's very exciting that we're actually working on both fronts at the University of Cincinnati, trying to find better treatments for glioblastoma," Forbes said.
Zucca reflected on her experience with this multidisciplinary effort: "It brings together molecular immunology, biomedical engineering and clinical neurooncology in a way that has profoundly influenced my development as a researcher," she said. "Most importantly, it represents a tangible step toward therapies that leverage the patient's own immune system to combat one of the most aggressive cancers known."
Other contributors include Kevin Haworth and David Plas.
