2 Small Clinical Trials Spark Cautious Hope in Glioblastoma Treatment

By Steve Blanchard - March 18, 2024

With a five-year survival rate of less than 10%, glioblastoma is one of the most aggressive forms of brain cancer. The disease gained national attention after claiming the lives of Edward Kennedy, John McCain and Beau Biden. It has no cure and has seen minimal progress in drug treatment over the past two decades.

But two clinical trials published this month in the New England Journal of Medicine and Nature Medicine offer a glimmer of hope. Both trials looked at the effects of chimeric antigen receptor T-cell therapy, or CAR T therapy, in patients whose glioblastoma returned following their initial treatment.

While the trials were very small, both showed that CAR T was safe and shrank tumors.

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"These results are preliminary but encouraging."

- Dr. Michael Vogelbaum, Department of Neuro-Oncology

“These results are preliminary but encouraging,” said Dr. Michael Vogelbaum, chief of neurosurgery and program leader of Neuro-Oncology at Moffitt Cancer Center.

In the study published in The New England Journal of Medicine, T cells were engineered to seek out and attack a mutated form of the protein EGRF called EGFRviii that’s often found in abundance in glioblastoma tumors but is not present in healthy brain tissue.

The trial published in Nature also had CAR T cells target EGFRviii, as well as another protein called IL13Rα2, which is found in 75% of glioblastoma tumors. Subsets of tumor cells may only produce one of the targets, so the dual treatment approach can collectively attack more of the tumor cells.

CAR T has proved to be effective for treating certain blood cancers. In those cases, a patient’s own immune cells are modified in a lab to seek out specific proteins and then reintroduced to the body. There, they replicate and create battalions of immune cells programmed to combat cancer.

“In general, immunotherapies have not shown any activity against glioblastoma,” Vogelbaum said. “Glioblastoma does not have a lot of the features that other cancers have that can stimulate an immune response.”

Vogelbaum described glioblastoma as being immunosuppressive, which impacts the entire immune system, as well as the brain tissue around the cancer cells.

“Glioblastoma stimulates portions of the immune system that normally act as checks against the immune system attacking normal tissues inappropriately,” he said. “The immune system, in a general sense, has accelerators and brakes. A lot of the immunotherapies that have been successful in treating other cancers act to remove those brakes.”

Others, he added, work to push down on the accelerator. Finding the right combination of the two is the challenge in finding impactful immunotherapy for glioblastoma.

“We are trying to piggyback on all of the exciting developments in other forms of cancer to see if we can develop those therapeutics in glioblastoma,” Vogelbaum said. “Any time we see an early response, we all get very excited about that, no question. These initial clinical responses can point to a direction of further research to achieve durable responses and maybe even cures.”

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