New cell therapy wipes out aggressive childhood brain cancer in mice
Researchers at the University of California, San Francisco (UCSF) have developed B-SYNC CAR-T, an immune cell therapy that activates only inside the brain. It eliminated diffuse midline glioma in mice, and human trials could begin as early as April 2027.
Scientists at the University of California, San Francisco (UCSF) have developed a new immune cell therapy that switches on only after it reaches the brain. In experiments on mice, the engineered cells completely eliminated diffuse midline glioma (DMG), an aggressive childhood brain cancer. The results were published on October 28 in Science Translational Medicine, and the team is preparing first clinical trials in people, which could start as early as April 2027.
DMG grows in the brainstem, which controls breathing, heartbeat and swallowing, and spreads into surrounding healthy tissue. Nearly all children diagnosed with it die within a year, and current treatments have done little to halt its progression.
How the therapy works
The therapy is called B-SYNC CAR-T. In standard CAR-T treatment, a patient's T cells, a type of immune cell, are modified to carry special receptors known as CARs, which recognize proteins on cancer cells and trigger an attack. This approach has so far struggled against brain tumors.
B-SYNC cells are programmed to produce CARs only when they detect brevican, a protein found naturally throughout the brain. Once active, they hunt for cancer cells carrying the proteins EphA2 or IL13Rα2. The system builds on an earlier therapy, E-SYNC, designed for glioblastoma, which relied on a mutation present in only about 20% of patients.
Results in mice
When the cells were given intravenously, some reached the brain and began attacking tumor cells, while cells in the blood and spleen did not produce CARs. When the therapy was injected directly into the brain's ventricles, the cancer was completely eliminated in every mouse tested, across two models with human DMG tumors. Conventional CAR-T cells could not control the tumors.
About seven weeks after treatment, researchers introduced fresh DMG cells, and every treated mouse rejected them. B-SYNC cells remained functional more than 70 days later. The team suggests that avoiding early activation may limit T cell exhaustion, though the exact reason is unclear.
Next steps
The first trial will be led by UCSF physicians Marie Jaeger-Krause and Sabine Mueller and will use each patient's own T cells. Researchers plan to test different combinations of intravenous and direct brain delivery, including an implanted shunt for repeated doses. The therapy's effectiveness in humans has not yet been tested.
