Scientists eliminated aggressive childhood brain cancer in every mouse tested using an experimental immune cell therapy designed to become activated only after it enters the brain.
The findings could indicate a new way to treat diffuse midline glioma (DMG), a devastating cancer for which virtually no effective treatment options are available. However, experts caution that the results have so far only been demonstrated in mice and will need to be tested for safety and effectiveness in humans.
Dr Lucy Hooper, MD and co-founder of Coyne Medical, said News week: “CAR-T cell therapies have revolutionized the treatment of certain blood cancers, so it is very exciting to see work showing a possible way to extend this success to brain tumors. Diffuse midline glioma is a devastating childhood cancer, with a very high mortality rate and very limited treatment options.
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“What’s particularly interesting here is how researchers engineered T cells, a type of immune cell, with a biological switch called synNotch,” she added. “This responds to a signal in the brain before activating the cells’ cancer-targeting machinery. The goal is to focus treatment where it is needed and reduce the risk of damaging healthy tissue elsewhere in the body.”
Targeting a deadly childhood cancer
DMG develops in the brainstem, which controls critical functions such as breathing, heart rate and swallowing. Almost all children diagnosed with the disease die within a year, and existing treatments have done little to stop its progression.
Researchers at UC San Francisco developed the investigational treatment, known as B-SYNC CAR-T, to address some of the problems that limit CAR-T treatment for brain tumors.
CAR-T therapy involves genetically modifying a patient’s T cells so that they carry receptors that recognize proteins on cancer cells and trigger an immune attack. B-SYNC adds another layer of control.
Researchers identified brevican, a protein distributed throughout the brain, and redesigned the synNotch system so that its exposure triggers cells to produce cancer-targeting CAR receptors. Once activated in the brain, the cells can hunt tumor cells carrying proteins called EphA2 or IL13Rα2.
This means that the modified cells use the brain environment itself as an activation signal, rather than depending on a particular tumor mutation.
Tumors eliminated in each mouse
B-SYNC was initially developed for glioblastoma, but researchers recognized that it could potentially target DMG because both cancers typically display EphA2 and IL13Rα2.
When B-SYNC cells were given intravenously to mice implanted with human DMG cells, some entered the brain and began producing cancer-targeting receptors. Cells elsewhere in the body, including the blood and spleen, did not appear to activate them.
The researchers then introduced the cells directly into the fluid-filled ventricles of the brain. In two mouse models containing human DMG tumors, B-SYNC completely eliminated the cancer in each treated mouse. Conventional CAR-T cells were unable to control tumors.
The protection also persisted. Nearly seven weeks later, the researchers reintroduced the DMG cells and all of the treated mice rejected them. B-SYNC cells remained functional for more than 70 days after treatment.
“It has been difficult to produce CAR-T cells that can overcome DMG without causing unacceptable side effects,” Hideho Okada, professor of neurological surgery at UCSF and co-author of the study, said in a statement. “By limiting CAR expression of B-SYNC to when and where it matters – in the brain – we saw consistent and complete shutdown of DMG tumors in the laboratory.”
Okada and his fellow researchers are currently working on human tests using patients’ own genetically modified T cells. A clinical trial at UCSF Health could begin as early as April 2027.
Hooper added: “The tumor clearance observed in these mouse experiments is very encouraging, but this is still preliminary research. We need clinical trials to determine whether this approach can work safely and effectively in children. It offers a promising direction for a disease where better treatments are desperately needed. »
News week contacted the study authors by email for more information.
Reference
Lakshmanachety, S. et al. (2026). Brain-sensing synNotch-CAR T cells enable precise targeting and elimination of diffuse midline gliomas in multiple preclinical models. Science Translational medicine. https://doi.org/10.1126/scitranslmed.aed9994.
Contact Newsweek editors on this story: Kara Dolman and Cristina Diciu.
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