A nanoparticle and inhibitor trigger the immune system, outsmarting brain cancer: The approach, studied in mice, overcomes the blood brain barrier and breaks the shield tumors build against the immune response

Scientistsat the University of Michigan Rogel Cancer Center were optimistic when they identified a small molecule that blocked a key pathway in brain tumors. But there was a problem: How to get the inhibitor through the bloodstream and into the brain to reach the tumor.

In collaboration with multiple labs, the teams fabricated a nanoparticle to contain the inhibitor, and the results were even better than expected.

Not only did the nanoparticles deliver the inhibitor to the tumor in mouse models, where the drug successfully turned on the immune system to eliminate the cancer, but the process triggered immune memory so that a reintroduced tumor was also eliminated — a sign that this potential new approach could not only treat brain tumors but prevent or delay recurrences.

“No one could get this molecule into the brain. It’s really a huge milestone. Outcomes for patients with glioma have not improved for the last 30 years,” said Maria G. Castro, Ph.D., R.C. Schneider Collegiate Professor of Neurosurgery at Michigan Medicine. Castro is the senior author of the study, published in ACS Nano.

“Despite survival gains in many cancer types, glioma remains stubbornly challenging, with only 5% of patients living five years after their diagnosis,” said study author Pedro R. Lowenstein, M.D., Ph.D., Richard C. Schneider Collegiate Professor of Neurosurgery at Michigan Medicine.

Gliomas are often resistant to traditional therapies, and the environment inside the tumor suppresses the immune system, rendering new immune-based therapies ineffective. Add to that the challenge of passing the blood brain barrier, and it becomes even more difficult to deliver effective treatments to these tumors.

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