UCSF CAR-T Cells That Switch On Only in the Brain Clear a Deadly Childhood Tumor in Mice
Researchers at the University of California, San Francisco (UCSF) have engineered a CAR-T cell therapy called B-SYNC that stays dormant as it travels through the body and switches on only after it reaches the brain. In mouse experiments it cleared diffuse midline glioma (DMG), a lethal childhood brain cancer. The study was published October 28 in Science Translational Medicine.
DMG infiltrates the brainstem, which controls breathing, heartbeat and swallowing, and children almost always die within a year of diagnosis. There are almost no effective treatments, and conventional CAR-T cells have failed against this tumor.
B-SYNC's key is a molecular switch that senses brevican, a protein found throughout the brain. The team first gave B-SYNC cells intravenously to mice implanted with human DMG cells, then delivered the cells directly into the brain's ventricles. In two human DMG models, the treatment cleared tumors in every mouse tested, while conventional CAR-T cells again failed to control the cancer.
The therapy also showed staying power. Nearly seven weeks later, the team gave the treated mice a second round of cancer cells, and every mouse rejected the new tumors; the cells remained functional more than 70 days after treatment.
The work was led by UCSF neurological surgery professor Hideho Okada and cellular and molecular pharmacology professor Wendell Lim, with postdoctoral researcher Senthilnath Lakshmanachetty as first author. The team is preparing a clinical trial at UCSF Health that could begin as early as April 2027, led by physicians Marie Jaeger-Krause and Sabine Mueller, testing combinations of ventricular and intravenous delivery. The researchers stress that the results are preclinical and the therapy has not yet been tested in people.
(Source: University of California, San Francisco)
Source: University of California, San Francisco
Published by GSM · USA (original Chinese edition)
Photo: 图：加州大学旧金山分校的 Bakar 精准癌症医学大楼入口。 / Photo: The entrance of UCSF's Bakar Precision Cancer Medicine Building. (Wikimedia Commons, CC BY 4.0)
