Researchers at the University of Cincinnati Cancer Center are investigating a novel approach to treating glioblastoma, an aggressive form of brain cancer, using a slow-release wafer containing an immunostimulatory molecule. The research, supported by a Ride Cincinnati grant of $40,000, aims to stimulate the central nervous system’s (CNS) immune response following surgical removal of the tumor.
Glioblastoma is the most common primary cancer originating in the brain. Despite treatment, the prognosis remains poor, with only 5% to 7% of patients surviving five years after diagnosis, according to Dr. Jonathan Forbes, principal investigator of the project and an associate professor in the Department of Neurosurgery at the University of Cincinnati’s College of Medicine.
Historically, effective treatments for glioblastoma have been elusive due to significant biological challenges. One major hurdle is the blood-brain barrier, which protects the brain from harmful substances but also prevents many medications, particularly those with high molecular weight, from reaching tumor cells. Another challenge lies in the CNS’s typically “cold” immune microenvironment, which hinders the body’s natural ability to mount an immune attack against remaining cancer cells after surgery.
Currently, neurosurgeons utilize wafers that release radiation or general cell-killing agents. However, Dr. Forbes notes these treatments are nonspecific, costly, and have not demonstrated substantial improvements in patient outcomes. “After surgery to remove the tumor, we have unencumbered access to a resection cavity that we know microscopically is invaded by tumor cells,” Dr. Forbes explained. “Why not use this access to enhance the central nervous system’s ability to clear residual tumor cells?”
The research team, including medical student Beatrice Zucca, focused on identifying a safe and potent immune-stimulating molecule. Their research led them to Interleukin-15 (IL-15). “IL-15 is exceptionally effective at activating immune populations that are critical for recognizing and killing cancer cells,” Zucca stated. “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 grant funding will be used to assess how the IL-15-containing wafer stimulates the immune system, utilizing a groundbreaking “glioblastoma-on-a-chip” technology developed in collaboration with Dr. Ricardo Barrile, assistant professor of biomedical engineering in UC’s College of Engineering and Applied Science.
Organ-on-a-chip technology creates miniaturized models of living organs, replicating specific disease conditions. Dr. Barrile explained the advantage of this approach: “Instead of testing drugs on flat plastic dishes or relying solely on animal models – which often fail to predict human results due to genetic disparities – we use 3D bioprinting and microfluidics to build a living model of a human organ.”
Dr. Barrile’s lab pioneered a model integrating human brain cells with glioblastoma cells using 3D and bioprinting techniques. This model also incorporates a bioprinted “blood vessel” channel to simulate drug delivery and a channel to replicate the immune system. “This provides a ‘human-relevant’ platform to test therapies safely and accurately before they reach a patient,” Dr. 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.”
This initial phase of the project will concentrate on the wafer’s impact on the immune response to glioblastoma cells. However, researchers believe it could also contribute to validating the glioblastoma-on-a-chip as a tool for personalized medicine. “We are building a platform that could eventually predict a specific patient’s response to immunotherapy,” Dr. Barrile explained. “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. We are essentially moving from a one-size-fits-all approach to a tailored-to-you strategy.”
Alongside this research, the University of Cincinnati Brain Tumor Center is also exploring methods to overcome the blood-brain barrier using navigated focused ultrasound, which can temporarily open the barrier to allow for better drug delivery. “It’s very exciting that we’re actually working on both fronts at the University of Cincinnati, trying to find better treatments for glioblastoma,” Dr. Forbes noted.
Zucca emphasized the collaborative nature of the research and its potential impact. “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.”
The project also includes contributions from Kevin Haworth and David Plas.
