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.
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."