Innovative Dual-Target CAR T Cell Therapy Shows Promise Against Aggressive Brain Cancer

A novel dual-target CAR T cell therapy has demonstrated potential in slowing the progression of glioblastoma, an aggressive form of brain cancer notorious for its rapid growth and poor prognosis. In a recent clinical trial, nearly two-thirds of patients experienced tumor reduction following treatment that involves injecting specially engineered immune cells directly into the cerebrospinal fluid. Although survival data are still being collected, some participants have survived beyond a year, which is significant given that the typical lifespan after recurrent glioblastoma diagnosis is less than a year.

Presented at the 2025 American Society of Clinical Oncology (ASCO) annual meeting and published in Nature Medicine, these findings build on early promising results from the same Phase I trial and align with other recent studies across the U.S. Glioblastoma, the most common and deadly adult brain cancer, usually recurs even after aggressive treatment, with median survival after recurrence ranging from 6 to 10 months.

The therapy employs a personalized immunotherapy approach using a patient’s own immune cells. Unlike traditional CAR T cell therapies, which have been more successful in blood cancers, this treatment targets two proteins commonly found in brain tumors: epidermal growth factor receptor (EGFR) and interleukin-13 receptor alpha 2 (IL13Rα2). The dual-target CAR T cells are administered through injections into the cerebrospinal fluid, aiming to attack tumors more effectively.

In the study involving 18 patients with recurrent glioblastoma, the tumors shrank in about 62% of cases where some tumor tissue remained after surgery. While most tumors relapsed within a few months, some patients showed sustained stability. Specifically, three patients with over a year of follow-up were still alive, with one experiencing no tumor growth for over 16 months despite advanced disease.

The researchers observed signs that the therapy stimulates the immune system. In one case, immune cells infiltrated the tumor and cleared it, with additional evidence from spinal fluid samples showing persistent CAR T cells months after treatment. This suggests a lasting immune response that could be optimized further.

Safety assessments indicated that around 56% of patients experienced manageable grade 3 neurotoxicity, with no unexpected severe side effects. The therapy was deemed feasible and safe, establishing the maximum tolerated dose for future studies. Researchers plan to investigate multiple doses to extend tumor control and are optimistic about applying this approach earlier in the disease course.

The promising safety profile and initial efficacy results support upcoming clinical trials, including testing in newly diagnosed glioblastoma patients. The ultimate goal is to improve outcomes and quality of life by making tumors more responsive to immune-based therapies, especially before they become resistant or recur.