New Way to Fight Brain Cancer Shows Promise

06:20 March 25, 2024

New Way to Fight Brain Cancer Shows Promise

A new way to fight an extremely aggressive kind of brain tumor is showing promise in two experiments with a small number of patients.

For the experiments, scientists took patients’ own immune cells and turned them into “living drugs” that can find and attack the tumor, called glioblastoma. Researchers have reported that, in early tests, the immune cells have made the tumors temporarily smaller.

The treatment is called CAR-T therapy. Doctors already use the treatment to fight blood-related cancers like leukemia. But researchers have struggled to make CAR-T therapy work for solid tumors.

Now, separate teams at both Massachusetts General Hospital and the University of Pennsylvania are developing next-generation CAR-T therapy treatments. They are designed to get past some of glioblastoma’s defenses.

University of Pennsylvania’s Dr. Stephen Bagley led one of the studies. He warned, “It’s very early days.” But he added, “We’re optimistic that we’ve got something to build on here…”

Glioblastoma is the brain cancer that killed U.S. President Joe Biden’s son Beau Biden. It also took the life of longtime Arizona Senator John McCain.

Glioblastoma is fast-growing and hard to treat. Patients usually live 12 to 18 months after diagnosis. Even after many years of research, there are few options if the cancer returns after treatments.

A kind of cell in the immune system called T cells fight disease, but cancer has ways to hide. With CAR-T therapy, doctors genetically change a patient’s own T cells so they can better find different cancer cells.

But solid tumors like glioblastoma have an additional difficulty. They contain mixtures of cancer cells with different mutations. Targeting just one kind still means the other kinds can keep growing.

The teams at Massachusetts General Hospital and University of Pennsylvania each developed a therapy with two different methods. They tried them in patients whose tumors returned after usual treatment.

At Massachusetts General Hospital, Dr. Marcela Maus and her team combined CAR-T with T-cell engaging antibody molecules. T-cell engaging antibody molecules are molecules that can attract nearby, regular T cells to join in the cancer attack. The result, called CAR-TEAM, targets a protein called EGFR. EGFR is found in most glioblastomas but not in normal brain tissue.

The University of Pennsylvania’s method was to create a two-target CAR-T therapy. It hunts for both the EGFR protein plus a second protein found in many glioblastomas.

Both teams administered the treatment through a medical device called a catheter into the fluid that surrounds the brain.

Massachusetts General Hospital tested three patients with its CAR-TEAM therapy. Brain imagining a day or two later showed their tumors were quickly becoming smaller. The researchers reported their findings in the publication the New England Journal of Medicine.

Maus said, “None of us could really believe it.”

Two of the patients’ tumors began to regrow soon. A second treatment given to one of them did not work. But one patient’s response to the experimental treatment lasted more than six months.

University of Pennsylvania researchers reported their findings in the publication Nature Medicine. They similarly found that in the first six patients given its therapy tumors got smaller. While some came back quickly, Bagley said one patient treated last August still has not had any regrowth.

For both teams, the goal is to see longer-lasting results.

Bagley said, “None of this is going to matter if it doesn’t last.”

I’m Gregory Stachel.

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