'Nano-immunotherapy' halts glioblastoma in mice

Brain
Glioblastoma is the most common brain tumor in adults but is difficult to treat because of challenges getting drugs across the blood-brain barrier. (VSRao / Pixabay)

One of the most difficult challenges in treating the brain cancer glioblastoma is that few drugs can pass through the blood-brain barrier. Scientists at Cedars-Sinai in Los Angeles have developed a system to circumvent this hurdle—one that combines a powerful immuno-oncology drug with a polymer-based delivery vehicle that can cross the blood-brain barrier.

The researchers showed that this “nano-immunotherapy” treatment crossed the blood-brain barrier in mouse models of glioblastoma, and that it stopped tumor cells from multiplying. They published their findings in the journal Nature Communications.

The Cedars-Sinai team used the polymer scaffold to deliver two types of immune checkpoint inhibitors, blocking either CTLA-4 or PD-1. When injected into the bloodstream of mice, the drugs quickly infiltrated brain tumors, but not healthy brain tissue, the researchers reported.  

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Brain tumors are normally able to suppress immune attacks using macrophages and T regulatory cells (Tregs). The Cedars-Sinai researchers observed that after they treated the mice with nano-immunotherapy, the checkpoint inhibitors blocked Tregs and macrophages. That allowed tumor-killing immune cells to flood in and treat the tumors.

Glioblastoma multiforme is the most common type of brain tumor in adults, accounting for 17% of all brain cancer diagnoses, according to the American Association of Neurological Surgeons. It’s a notoriously difficult tumor to treat, not only because of the challenge of getting drugs past the blood-brain barrier, but also because the cancer tends to spread rapidly and the brain has a limited ability to heal itself.

Several research groups are looking for workarounds in treating glioblastoma. Earlier this month, scientists from Brigham and Women’s Hospital and the Dana-Farber Cancer Institute announced promising early results from a phase 1 study of a gene-therapy approach that incorporates Ziopharm’s oral drug veledimex. And the Ivy Brain Tumor Center is testing combos that include Karyopharm Therapeutics’ recently approved Xpovio, a nuclear-export inhibitor.

Cedars-Sinai’s Julia Ljubimova, M.D., Ph.D., professor of neurosurgery and lead author of the new study, says further preclinical work will need to be done before the nano-immunotherapy approach can be tried in patients with glioblastoma. But she remains optimistic.

"The horizon for treatment of brain cancer is getting clearer," Ljubimova said in a statement. "We hope that by delivering multifunctional new-generation drugs through the blood-brain barrier, we can explore new therapies for many neurological conditions."

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