B-SYNC CAR-T Eliminates Diffuse Midline Glioma in Mice
Scientists at UC San Francisco developed a new type of immune cell therapy that activates only after entering the brain.
This precision approach allows engineered T cells to attack aggressive cancer while remaining inactive elsewhere in the body.
Diffuse midline glioma is an aggressive childhood brain cancer that spreads into surrounding healthy tissue and grows into the brainstem.
Engineering Smarter CAR-T Cells to Fight Brain Tumors
CAR-T therapy modifies a patient’s T cells to carry special receptors called CARs that recognize and attack proteins on cancer cells.
Unlike conventional CAR-T treatments, which have struggled against brain tumors, these modified immune cells are programmed to activate their cancer-fighting machinery specifically within the brain, said Hideho Okada.
A Molecular Switch Targeting Brain Proteins
The team redesigned their synNotch system to trigger CAR production only when it encounters brevican, a protein naturally distributed throughout the brain. These B-SYNC cells then search for tumor-associated proteins like EphA2 or IL13Rα2.
This mechanism lets the therapy operate without depending on a single tumor-specific mutation. Scientists suspect this targeted design makes the cells more effective, although the precise reason remains unclear.
Complete Tumor Elimination in Laboratory Tests
Researchers administered B-SYNC CAR-T cells intravenously and via intracerebroventricular injection into mice with DMG. The treatment completely eliminated the cancer in every mouse tested.
The researchers believe this approach performed better than conventional CAR-T therapies. B-SYNC cells outside the brain did not produce the CAR receptors, confirming the activation stayed localized.
That was just as we designed it,
said Lakshmanachetty.
Lasting Immune Activity Against Returning Cancer
Several weeks after the initial treatment, researchers introduced a new round of DMG cells to the treated mice. Every mouse rejected the new cancer cells, showing protective effects well beyond the initial tumor clearance.
B-SYNC cells remained functional more than 70 days after treatment. By preventing CAR activation until the cells reach the brain, B-SYNC may help preserve their strength against T cell exhaustion, a problem in which immune cells gradually lose their ability to attack cancer effectively.
We didn’t expect B-SYNC CAR-T cells to necessarily persist,
Lakshmanachetty said. But they are still patrolling for cancer over 70 days out — and they’re still very functional.
Clinical Trials Slated for April 2027
The promising laboratory results prompted the UCSF team to prepare for human clinical trials at UCSF Health. Testing could begin as early as April 2027.
Physicians Marie Jaeger-Krause, MD, and Sabine Mueller, MD, PhD, will lead the first trial.
Mice with DMG are being cured, and we are incredibly excited to bring this therapy to the children and young adults we care for. This is exactly the kind of innovative approach they deserve.
Frequently Asked Questions About B-SYNC Therapy
How does B-SYNC activate only inside the brain?
The engineered cells use a modified synNotch receptor system that triggers CAR production exclusively upon encountering brevican, a protein naturally found throughout the brain.
Why do traditional CAR-T treatments struggle against brain tumors?
Prolonged immune activation can also lead to T cell exhaustion, gradually weakening the cells’ ability to attack cancer.
Who will lead the upcoming clinical trials?
UCSF physicians Marie Jaeger-Krause, MD, and Sabine Mueller, MD, PhD, will lead the initial human clinical trials at UCSF Health starting potentially in April 2027.