Scientists test treatment strategy using ‘glioblastoma on a chip’
Project to test wafers loaded with signaling molecule to help kill cancer cells
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A team of scientists at the University of Cincinnati Cancer Center is embarking on a series of tests to evaluate an experimental immune-modulating treatment strategy for glioblastoma, an aggressive form of glioma, using a technology known as a glioblastoma-on-a-chip model.
Unlike traditional laboratory models, which grow cells in plastic dishes, these models use 3D printing and bioprinting to arrange different cell types in an architecture that mimics conditions in human tissue.
“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,” Riccardo Barrile, PhD, a University of Cincinnati professor who helped create the model, said in a university news story. “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.”
The researchers will test the effects of wafers loaded with interleukin-15 (IL-15), a signaling molecule that can increase the activity of cancer-killing immune cells. Beatrice Zucca, a medical student working on the project, said the molecule “is exceptionally effective at activating immune populations that are critical for recognizing and killing cancer cells.”
“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,” Zucca said.
Wafer implants could help clear cancer cells remaining after surgery
The theory is that these IL-15-loaded wafers could be implanted in the brain after surgery, helping stimulate immune cells to clear any remaining cancer cells and prevent the tumor from regrowing.
“After surgery to remove the tumor, we have unencumbered access to a resection cavity that we know microscopically is invaded by tumor cells,” said Jonathan Forbes, MD, a neurosurgeon at the university’s medical college and principal investigator on the project. “Why not use this access to enhance the central nervous system’s ability to clear residual tumor cells?”
Through their tests using glioblastoma-on-a-chip models, the researchers hope to better understand how wafers loaded with IL-15 modulate immune cell activity. A key feature of these models is that, unlike traditional cell culture models, they include immune cells alongside cancer cells, as does the human brain.
“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,” Barrile said.
Zucca said that the project “represents a tangible step toward therapies that leverage the patient’s own immune system to combat one of the most aggressive cancers known.”
The scientists also hope these lab models could serve as a platform for developing and testing more personalized treatment approaches.
“We are building a platform that could eventually predict a specific patient’s response to immunotherapy,” Barrile said. “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.”
The project is funded by a $40,000 grant from Ride Cincinnati, a grassroots bike tour that raises money for cancer research and care in the Ohio city.
