This CAR T-therapy for aggressive brain cancer in 18 patients

A new CART-T cell therapy has been shown, in a small clinical trial involving 18 patients, to slow tumor growth in a highly aggressive, fast-growing brain cancer. Tumors, according to a study published in Nature Medicine , shrank after the experimental CART-T cell therapy in nearly two-thirds of patients.

Although survival data are accumulating, some patients lived 12 months or more after receiving the investigational therapy , a very important finding since the typical survival for this patient population is less than one year.

The results, also presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, are based on the same Phase I clinical trial published last year and conducted by researchers at the Abramson Cancer Center (ACC) of the University of Pennsylvania and the Perelman School of Medicine of Pennsylvania .

Glioblastoma is the most common and deadly brain cancer in adults; it has an average life expectancy of 12 to 18 months after diagnosis, despite decades of specialized research. Even after aggressive treatment, the cancer grows back or recurs in almost all patients. The median survival rate for recurrent glioblastoma typically ranges from 6 to 10 months.

Before the trial, notes lead researcher Stephen Bagley, "Many of these patients had rapidly growing tumors, and the treatment changed the trajectory of their disease, which is very significant for patients with glioblastoma."

Dual-targeted CAR-T cell therapy is a form of personalized immunotherapy that uses a patient's own immune cells to treat their cancer. While it has been highly successful in blood cancers, CAR-T cell therapy has not yet made significant progress against solid tumors, such as brain cancer.

The new cell therapy is unique in that it targets not one, but two proteins common in brain tumors: the epidermal growth factor receptor (EGFR) and the interleukin-13 receptor alpha 2 (IL13Rα2), and is delivered by injection into the cerebrospinal fluid.

The study included 18 patients with recurrent glioblastoma who underwent surgery to remove as much of the tumor as possible, followed by infusion of the dual-targeted CAR T-cell therapy directly into the cerebrospinal fluid. Tumors shrank after CAR T-cell therapy in eight of the 13 patients (62%).

While tumors grew back after one to three months in most patients, encouraging signs were observed: two patients remain alive with stable disease that has continued for more than six months; of the seven patients with a follow-up time of at least 12 months, three were still alive after one year, including one person whose cancer has remained stable, with no tumor growth, for more than 16 months.

Another relevant aspect of the research is that the therapy remains in the immune system after infusion, preventing tumor growth over time.

O'Rourke notes that "periods of stability, when tumors shrink or stop growing, greatly improve a patient's quality of life. Our goal is to refine the treatment so more patients experience longer-lasting results."

"By the time glioblastoma recurs, treating it becomes even more difficult, and the patient has already been through so much," Bagley emphasizes. "We hope that by acting quickly to test this CAR T-cell therapy in the context of a new diagnosis, the cancer will be more susceptible to the therapy and more patients will benefit."