Researchers have reported early findings from a Phase I trial suggesting that repeated intracranial infusions of a CAR T-cell therapy targeting CD276 show promise for treating recurrent glioblastoma. The study, published in Nature, evaluated TX103, an autologous therapy developed by Fuzhou Tcelltech Biological Science and Technology. Investigators administered the treatment directly into the brain of 15 patients using implanted Ommaya reservoirs, delivering a total of 72 infusions across 13 treatment cycles.
CD276, also known as B7-H3, is a protein that sits on the surface of glioblastoma cells and the blood vessels that feed the tumor. Unlike earlier CAR T targets, this molecule appears not just on the cancer cells but also in the tumor’s supporting tissue. This dual expression makes it an attractive option for oncologists trying to overcome the heterogeneous nature of the disease. The therapy is designed to seek out these cells and trigger the body’s immune system to attack them.
The trial included patients with poor prognostic features, including unmethylated MGMT and TERT mutations. Because the therapy is administered directly into the central nervous system, immune activation remained largely confined to the brain. This method minimized systemic toxicity, though it did introduce localized neuroinflammation as a primary safety concern. Investigators noted no dose-limiting toxicities or treatment-related deaths, though three patients experienced grade 3 neurologic events that were managed with standard interventions.
One of the most difficult aspects of this trial was distinguishing between tumor progression and treatment-related inflammation. Nearly 80 percent of patients developed radiographic enlargement early in the process. However, some of these patients later saw their tumors regress. This pattern suggests that the immune system is active, but doctors must wait to see if that activity translates into long-term control.
For patients facing a diagnosis with a median survival of about 15 months, the potential for a therapy that can be given multiple times without cumulative toxicity offers a different kind of hope. The ability to return to the operating room or clinic for additional infusions provides a pathway for sustained intervention that many other treatments lack. The study design prioritized safety, yet the efficacy data was encouraging.
Correlative analyses indicated that CAR T cells expanded in the cerebrospinal fluid and produced robust cytokines. Higher levels of interferon-ฮณ signaling were linked to longer overall survival, suggesting that localized immune activation may s
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