New technology guides immune system cells to fight brain cancer and multiple sclerosis

Researchers have found a way to program immune system cells to attack glioblastoma and treat MS inflammation in mice. The technology will soon be tested in a clinical trial for people with glioblastoma.

UCSF scientists have developed a “molecular GPS” that guides immune cells to the brain and kills tumors without harming healthy tissue.

This living cell therapy can be navigated through the body to a specific organ, addressing what has until now been a major limitation of CAR-T cancer therapies. The technology worked in mice, and the researchers expect it to be tested in a clinical trial next year.

Scientists have shown how immune cells could eradicate a deadly brain tumor called glioblastoma and prevent recurrences. They also used the cells to fight inflammation in a mouse model of multiple sclerosis.

“Living cells, especially immune cells, are adapted to move around the body, sense where they are, and find their targets,” said Wendell Lim, PhD, UCSF professor of cellular and molecular pharmacology and co-senior author of work. appears in Science on December 5.

Navigation to the source of the disease

Nearly 300,000 patients are diagnosed with brain cancer each year in the United States, and it is the leading cause of cancer death in children.

Brain cancers are among the most difficult cancers to treat. Surgery and chemotherapy are dangerous, and drugs can’t always get into the brain.

To overcome these problems, scientists developed a “molecular GPS” for immune cells that guided them with a “zip code” for the brain and a “street address” for the tumor.

They found the ideal molecular zip code in a protein called brevican, which helps form the jelly-like structure of the brain and only occurs there. To guide the way, they used two proteins found in most brain cancers.

The scientists programmed the immune cells to attack only if they first detect brevican and then detect one or the other of the brain cancer proteins.

Once in the bloodstream, they easily navigated into the mouse brain and eliminated a growing tumor. The immune cells that remained in the bloodstream remained dormant. This prevented it from attacking tissues elsewhere in the body that happened to have the same protein “address”.

A hundred days later, the scientists introduced new cancer cells into the brain, and enough immune cells remained to find and kill them, a good indication that they might be able to prevent any remaining cancer cells from development.

Brain-derived CAR-T cells were very, very effective at clearing glioblastoma in our mouse models, the most effective intervention we’ve seen in the lab. It shows how well GPS ensured that they would only work in the brain. The same strategy even worked to clear brain metastases from breast cancer.”

Milos Simic, PhD, the Valhalla Foundation Cell Design Fellow and co-first author of the paper

In another experiment, researchers used the brain’s GPS system to engineer cells that deliver anti-inflammatory molecules to the brain in a mouse model of multiple sclerosis. The modified cells reached their target and the inflammation subsided.

Scientists hope this approach will soon be ready for patients with other debilitating diseases of the nervous system.

“Glioblastoma is one of the deadliest cancers, and this approach is poised to give patients a fighting chance,” said Hideho Okada, MD, a UCSF oncologist and co-senior author of the paper.

“Between cancer, brain metastases, immune disease and neurodegeneration, millions of patients could one day benefit from targeted brain therapies like the one we’ve developed.”