A new Stanford Medicine-led study, published May 12 in Cell, has identified a link between CAR-T cell therapy and mild cognitive impairments—often described by patients as “brain fog.” This includes symptoms like forgetfulness and difficulty concentrating. The study, primarily conducted in mice, reveals that CAR-T therapy alone can trigger these cognitive issues, independent of other cancer treatments.
Key Findings
Mechanism Identified: The cognitive issues are driven by activation of brain immune cells (microglia), which release inflammatory signals. These signals damage oligodendrocytes, the cells responsible for producing myelin, impairing nerve signal transmission.
Broad Impact: Mice with cancers originating in or outside the brain exhibited cognitive decline after CAR-T therapy—except those with bone cancer, which caused minimal immune activation.
Shared Pathway: The same mechanism underlies brain fog caused by chemotherapy, radiation, and respiratory infections like COVID-19 and influenza.
Promising Solutions
Two potential treatments successfully reversed the cognitive symptoms in mice:
Temporary microglia depletion, which led to the return of non-reactive microglia and restored cognitive function.
Blocking chemokine signaling, using a brain-penetrating drug to inhibit harmful immune pathways.
Human Evidence
Postmortem brain tissue from clinical trial participants confirmed the presence of similar microglial and oligodendrocyte abnormalities in humans, supporting the relevance of the mouse model findings.
Dr. Michelle Monje, senior author and professor of pediatric neuro-oncology, emphasized the need to understand and address these long-term side effects:
“We are seeing long-term survivors after CAR-T therapy… Now we must develop therapeutic approaches to fix this newly recognized syndrome.”
The team is now working on translating these treatments into safe clinical applications.
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