A new strategy to attack aggressive brain cancer shrinks tumors in two early trials

Washington: A new strategy to fight an extremely aggressive type of brain tumor showed promise in a pair of experiments with a handful of patients.

Scientists took patients’ own immune cells and turned them into “living medicines” capable of recognizing and attacking glioblastoma. In Phase 1 trials, those cells shrank tumors, at least temporarily, researchers reported Wednesday.

So-called CAR-T therapy is already used to fight blood-related cancers such as leukemia, but researchers have struggled to make it work for solid tumors. Now separate teams at Massachusetts General Hospital and the University of Pennsylvania are developing next-generation CAR-T versions designed to overcome some of glioblastoma’s defenses.

“It’s very early days,” cautioned Penn’s Dr. Stephen Bagley, who led one of the studies. But “we’re optimistic that we’ve got something to build on here, a real foundation.”

Glioblastoma, the brain cancer that took the lives of President Joe Biden’s son Beau Biden and longtime Arizona senator John McCain, is fast-growing and hard to treat. Patients typically survive 12 to 18 months after diagnosis. Despite decades of research, few options exist when it comes to relapse after surgery and radiation.

The immune system’s T cells fight disease but cancer has ways of hiding. With CAR-T therapy, doctors genetically modify a patient’s own T cells so that they can better seek out specific cancer cells. Yet, solid tumors such as glioblastoma pose an additional obstacle – they contain a mixture of cancer cells with different mutations. Targeting only one type allows the rest to continue growing.

Mass General and Penn developed two-pronged approaches and tried them in patients whose tumors regressed after standard treatment.

At Mass General, Dr. Marcella Maus’s lab combined CAR-Ts with T-cell attractant antibody molecules – molecules that can attract nearby regular T cells to join the cancer attack. The results, called CAR-Team, target versions of a protein called EGFR that is found in most glioblastomas but not in normal brain tissue.

Penn’s approach was to create a “dual-target” CAR-T therapy that looks for both the EGFR protein and a second protein found in many glioblastomas.

Both teams injected the treatment through a catheter into the fluid bathing the brain.

Mass General tested three patients with its CAR-Team, and brain scans a day or two later showed that their tumors began to shrink rapidly, researchers reported in the New England Journal of Medicine.

“None of us could really believe it,” Maus said. “Doesn’t happen like this.”

Two patients’ tumors soon began to grow back, and in one of them, repeated doses did not work. But one patient’s response to the experimental treatment lasted more than six months.

Similarly, Penn researchers reported in Nature Medicine that the first six patients given its therapy experienced varying degrees of tumor shrinkage. While some recovered quickly, Bagley said one treated in August has yet to see a regrowth.

The challenge for both the teams is to maintain it for a long time.

“It’s not going to make a difference if it doesn’t stick,” Bagley said.

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