Scientists have created a “molecular GPS” that guides immune cells into the brain to effectively destroy tumors while sparing healthy tissue.
Researchers have successfully programmed immune cells to combat glioblastoma and manage inflammation caused by multiple sclerosis in mice, with plans to test this technology in a clinical trial for human patients with glioblastoma shortly.
At UCSF, scientists developed a “molecular GPS” that directs immune cells to the brain to target tumors without damaging healthy surrounding tissue.
This innovative cell therapy can maneuver through the body toward specific organs, overcoming a significant hurdle that CAR-T cancer therapies previously faced. The technology has shown promise in mice and is expected to enter clinical trials next year.
The research demonstrated that immune cells could successfully destroy glioblastoma, a particularly aggressive form of brain cancer, and prevent its return. Additionally, the cells were able to reduce inflammation in a mouse model simulating multiple sclerosis.
“Living cells, particularly immune cells, are naturally designed to move throughout the body, sense their surroundings, and locate their targets,” noted Wendell Lim, PhD, a UCSF professor of cellular and molecular pharmacology and co-senior author of the study published in Science on December 5.
Finding the source of illness
Each year, close to 300,000 individuals in the United States are diagnosed with brain cancer, making it a leading cause of cancer deaths in children.
Brain cancers are notoriously difficult to treat; surgical and chemotherapy options come with significant risks, and drugs often struggle to penetrate the brain.
To address these challenges, researchers created a “molecular GPS” for immune cells, equipping them with a “zip code” specific to the brain and a “street address” for the tumor.
They identified a unique molecular zip code within a protein called brevican, which contributes to the brain’s gel-like structure and is only located there. For the tumor’s street address, they utilized two proteins commonly found in various brain cancers.
The researchers programmed the immune cells to start attacking only if they first recognized brevican and subsequently detected one of the brain cancer-associated proteins.
Once in the bloodstream, these immune cells navigated to the brain effortlessly, successfully targeting and eliminating the tumor. The immune cells that remained in circulation stayed inactive, preventing any other tissues with similar protein “addresses” elsewhere in the body from being attacked.
After 100 days, the researchers introduced additional tumor cells into the brain, and enough immune cells remained to identify and eliminate them, indicating their potential to stave off any leftover cancer cells from regrowing.
“The brain-primed CAR-T cells effectively targeted and cleared glioblastoma in our mouse models, showcasing the most successful intervention we’ve observed in the lab so far,” said Milos Simic, PhD, a Valhalla Foundation Cell Design Fellow and co-first author of the paper. “This highlights how effectively the GPS directed them to work solely in the brain. The same approach was also effective against breast cancer brain metastases.”
In another study, researchers utilized the brain GPS system to create cells that transport anti-inflammatory molecules to the brain in a mouse model of multiple sclerosis, resulting in targeted delivery and a reduction in inflammation.
The scientists are optimistic that this strategy will soon be applicable for patients suffering from various debilitating nervous system conditions.
“Glioblastoma is one of the most lethal forms of cancer, and this method may provide patients with a viable chance for treatment,” said Hideho Okada, MD, a UCSF oncologist and co-senior author of the paper.
“With the potential to address cancer, brain metastases, immune disorders, and neurodegeneration, millions of patients could benefit from specialized brain therapies like the one we’ve created.”
