Scientists eliminate fatal childhood brain tumors in mice with targeted CAR-T therapy
Researchers at the University of California, San Francisco have engineered a targeted immunotherapy capable of eliminating diffuse midline glioma (DMG), an aggressive childhood brain cancer that is almost always fatal within a year. In findings published October 28 in Science Translational Medicine, the novel treatment—designated B-SYNC CAR-T—completely eradicated tumors across two mouse models and provided durable protection, preventing new tumor formation when cancer cells were reintroduced weeks later.
Traditional CAR-T therapies often struggle against brainstem tumors or trigger dangerous off-target side effects. To solve this, researchers Hideho Okada and Wendell Lim utilized a synNotch molecular switch that keeps the modified T cells dormant until they encounter brevican, a protein naturally distributed across the brain. Once inside brain tissue, the cells switch on to target two cancer-associated proteins, EphA2 and IL13Rα2. This approach overcomes a key flaw in their earlier E-SYNC platform, which relied on an EGFRvIII mutation found in only about 20% of patients.
Because activation depends on a brain-specific marker rather than a variable cancer mutation, the therapy can target DMG more reliably without damaging peripheral organs. Following these successful laboratory trials, the researchers are preparing for clinical trials at UCSF Health, which could begin as early as April 2027.
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