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Mass General Researchers Report Major Breakthrough in Deadly Brain Cancer Treatment

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Researchers at the Mass General Cancer Center reported a breakthrough in treatment for glioblastoma in a March 13 paper published in the New England Journal of Medicine.

Glioblastoma, the most aggressive type of brain cancer, accounts for half of all primary malignant brain tumors with 10,000 Americans dying due to the cancer every year.

To fight cancer, researchers have focused on harnessing the power of CAR-T cells, which are genetically engineered receptor immune cells that bind to and kill cancer cells.

Although CAR-T cells previously revolutionized treatment for blood cancers, they have “had limited success” for glioblastoma treatments, according to Bryan D. Choi ’06, a neurosurgeon at MGH and a co-author on the paper.

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But Choi and his team’s breakthrough discovery engineered CAR-T cells that dramatically reduced tumor presence in clinical trials of glioblastoma patients. Since the early 2000s, cancer centers have developed CAR-T cells designed to kill a common therapeutic target for glioblastoma, known as EGFRvIII — though the approach had only limited success.

Harvard Medical School professor Bob S. Carter, a co-author on the study, said Choi’s new approach — termed secondary targeting — makes the treatment more effective.

“One of the exciting things about this particular treatment is that it allows the targeting of the cancer cell by the therapeutic — in this case a T-cell — to be very highly specifically directed to an individual patient’s mutational profile,” he said.

The researchers are able to achieve this specificity through secondary targeting. The CAR-T cell first attaches to the tumor to kill the specific mutation and then recruits an army of the patient’s native T-cells to further attack the cancer.

When the treatment was first put into practice, the team was shocked by the results.

“It was actually hard to believe what we were seeing,” Choi said. “To be fair, we still don’t fully understand it. It’s something that we haven’t really seen with any form of therapy before.”

This new approach to cancer treatment stems from a collaboration between several specialties including neurosurgery, oncology, and neuro-oncology, according to Choi.

“This would not have happened if any single subgroup of that collaboration tried to do it — it really needed to be a team approach,” Carter added.

Although the treatment showed promise in the clinical trials in effecting short-term tumor reduction, the tumors eventually began to progress again.

Choi said future research efforts will be focused on making responses to the treatment more durable.

“We think that that might be achieved through combination with chemotherapy regimen,” he said.

Johns Hopkins University Director of Neurosurgery Henry Brem praised the study for “opening a new door” to the way brain tumors are treated.

“It’s truly breakthrough work. And it’s very, very significant for our field,” Brem said.

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