Experts have combined ‘glioblastoma-on-a-chip’ technology with wafer technology to enhance surgical outcomes for brain cancer patients.
A multidisciplinary team at the University of Cincinnati Cancer Centre has secured funding to develop a delayed-release immunostimulatory wafer to activate the CNS immune system following glioblastoma surgery.
Only 5-7% of patients with glioblastoma survive five years after diagnosis, and effective treatments have remained hard to develop for decades, mainly because of two major challenges: the blood-brain barrier, which protects the brain from harmful bacteria but also prevents high-molecular-weight drugs from reaching tumour cells.
Additionally, the CNS’s ‘cold’ immune microenvironment makes it more difficult to stimulate an immune response capable of destroying cancer cells that infiltrate the brain and cannot be surgically removed.
Jonathan Forbes, associate professor and residency director at UC’s Department of Neurosurgery and neurosurgeon at UC Gardner Neuroscience Institute, explained that current wafers can release radiation or cell-killing agents but are non-specific, costly, and do not greatly improve patient outcomes.
‘After surgery to remove the tumour, we have unencumbered access to a resection cavity that we know microscopically is invaded by tumour cells. Why not use this access to enhance the central nervous system’s ability to clear residual tumour cells?’
Last autumn, medical student Beatrice Zucca worked as a neuro-oncology research fellow under Forbes’s supervision. She said the first step was to determine which immune-stimulating molecule was safe and potent enough to activate the brain’s immune system, leading to the discovery of the protein interleukin-15 (IL-15).
‘IL-15 is exceptionally effective at activating immune populations that are critical for recognising and killing cancer cells. It improves their survival, expands their numbers, and boosts their cell-killing functions, making it an ideal candidate to drive a coordinated immune attack against a highly resistant cancer like glioblastoma.’
The new grant funding will enable the team to test how the immunostimulatory preparation influences the immune system using glioblastoma-on-a-chip technology developed in collaboration with Ricardo Barrile, an assistant professor of biomedical engineering at UC’s College of Engineering and Applied Science.
He said: ‘An organ-on-a-chip is a miniaturised model of a living organ designed to incorporate the minimal biological elements needed to replicate specific disease conditions. 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 construct a living model of a human organ.’
Barrile’s team was the first to develop a model that combines human brain cells with glioblastoma cells using a mix of 3D printing and bioprinting. The glioblastoma-on-a-chip model includes a bioprinted ‘blood vessel’ channel to simulate drug delivery from the bloodstream to the brain, as well as a channel to imitate the immune system.
He explained: ‘This provides a “human-relevant” platform to test therapies safely and accurately before they reach patients. Integrating the immune system was the missing element and is crucial for replicating the natural composition of glioblastoma, which, in patients, can comprise up to 30% immune cells. These cells are often lost during in vitro cell culture.’
While this phase focuses on how the wafer impacts the immune response to glioblastoma cells, it may also advance the validation of Barrile’s glioblastoma-on-a-chip as a personalised medicine tool.
