Study Reveals Mild Cognitive Side Effects of CAR-T Cell Therapy in Cancer Patients

A recent study led by Stanford Medicine has identified that CAR-T cell therapy, a groundbreaking immunotherapy for cancer, can lead to mild cognitive impairments often described as 'brain fog'. The research, primarily conducted on mice, demonstrates that these cognitive issues are caused by the same immune response mechanisms seen in other conditions such as chemotherapy and respiratory infections like COVID-19 and influenza. Patients undergoing CAR-T therapy may experience forgetfulness and concentration difficulties, which, although typically mild, can significantly impact quality of life and may not resolve spontaneously.

The study highlights that activation of microglia—immune cells in the brain—leads to the production of inflammatory molecules called cytokines and chemokines. These substances damage oligodendrocytes, the cells responsible for producing myelin, the insulating layer around nerve fibers that facilitates efficient nerve signal transmission. Such damage correlates with cognitive impairment.

Importantly, the team confirmed these mechanisms in human tissue samples obtained from patients in ongoing clinical trials. They also discovered potential strategies to mitigate these effects. In mice, transient depletion of microglia or blocking chemokine signals successfully restored cognitive function, suggesting promising avenues for future treatments.

With CAR-T cell therapy approved since 2017 for conditions like acute lymphoblastic leukemia, understanding its long-term effects is crucial. This research underscores the importance of developing medications to counteract cognitive side effects, especially as immunotherapy continues expanding into treating other cancers, including brain tumors. Researchers emphasize that addressing brain fog can improve patient recovery and overall well-being.

While the study confirms that the cognitive impact of CAR-T therapy is generally mild, its effects on developing brains, particularly in children, warrant further investigation. By elucidating the underlying cellular and molecular pathways, the findings pave the way for therapeutic interventions that could enhance the quality of life for cancer survivors post-treatment.

Source: https://medicalxpress.com/news/2025-05-car-cell-therapy-cancer-brain.html