A Gilead Sciences-backed CAR-T cell therapy demonstrated unprecedented tumor shrinkage in patients with recurrent glioblastoma, achieving a 62% response rate in a disease notorious for its resistance to treatment. The results, presented at the American Society of Clinical Oncology meeting in Chicago and published in Nature Medicine, represent a significant breakthrough for the most common and deadly brain tumor in adults.
Dual-Target Approach Addresses Tumor Complexity
The experimental therapy, developed by researchers at the University of Pennsylvania and Gilead's Kite cell therapy unit, employs a dual-target strategy to overcome glioblastoma's defensive mechanisms. Unlike traditional CAR-T treatments that target a single antigen, this approach simultaneously targets EGFR, found in 50% to 60% of glioblastoma tumors, and interleukin-13 receptor alpha 2, present in approximately 75% of cases.
"Solid tumors such as glioblastoma tend to have multiple subpopulations of tumor cells, suggesting that treatments will need more than one target to succeed," explained Dr. Stephen Bagley, the University of Pennsylvania researcher who led the study.
The treatment involves engineering patients' own white blood cells to recognize and kill cancer cells, then injecting these modified cells directly into spinal fluid to reach the brain tumor.
Clinical Results Show Promise Despite Limitations
The study included 18 patients with recurrent glioblastoma who had exhausted standard treatment options including surgery, radiation, and chemotherapy. Of the 13 patients with measurable tumors at treatment initiation, eight experienced tumor shrinkage—a remarkable outcome for a cancer that typically shows no response to available therapies.
"That was pretty remarkable to us because historically for recurrent glioblastoma tumors, we usually don't see anything shrink them," Bagley noted.
Several patients survived 12 months or longer, with one patient maintaining stable disease for 16 months. These survival outcomes contrast sharply with the typical six to 10-month prognosis for advanced glioblastoma patients whose cancers return after initial treatment.
However, the therapeutic benefit proved largely temporary, with many patients experiencing disease relapse within two to three months. Most patients developed manageable side effects including fevers and neurotoxicity such as lethargy or confusion lasting two to three days post-injection.
Next-Generation Development and Expansion Plans
Recognizing the persistence challenge, Kite is developing an enhanced version incorporating a third target designed to extend the therapy's duration in the brain. "We will be putting that construct into the clinic sometime next year," said Cindy Perettie, executive vice president of Gilead's Kite cell therapy unit.
The team also plans to evaluate the therapy in 12 patients with newly diagnosed glioblastoma. "We know patients in the frontline setting are going to be healthier," Perettie explained, expressing hope for more persistent therapeutic responses in this population.
Patient demand has been extraordinary, with Perettie estimating 10 times more patients seeking enrollment than available trial slots. Physicians are referring patients from locations as distant as Hawaii, reflecting the desperate need for effective glioblastoma treatments.
"Today, there's only one approved therapy outside of radiation, so for these patients, this is really exciting to see any kind of response," Perettie emphasized.
Kite plans to expand the triple-target version to three or four treatment centers, building on the current single-center experience. The development represents part of broader efforts to extend CAR-T therapy beyond blood cancers into solid tumors, where the technology faces additional challenges including tumor heterogeneity and immunosuppressive microenvironments.
"I think we're on the right track," Bagley concluded, expressing optimism that longer-lasting treatments will emerge within the next few years.
