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A new study led by Stanford University scientists has uncovered a previously underappreciated side effect of CAR-T cell therapy-a cutting-edge cancer treatment-revealing that recipients may experience mild cognitive issues, commonly described as “brain fog.”
CAR-T cell therapy, which involves genetically engineering a patient’s own immune cells to better recognize and attack cancer, has been hailed as a breakthrough for aggressive cancers. However, the Stanford-led research, published in the journal Cell, found that the therapy can lead to mild cognitive impairments such as forgetfulness and difficulty concentrating, even when the cancer is not located in the brain.
The study primarily used mouse models with tumors in various locations-including the brain, skin, blood, and bone-to assess the impact of CAR-T therapy on cognition. Standard memory and navigation tasks revealed that most mice developed symptoms of mild cognitive impairment after treatment, regardless of tumor location. The exception was mice with bone cancer that caused minimal inflammation, suggesting that the cognitive effects are linked more to the immune response than to the tumor’s proximity to the brain.
Researchers pinpointed the brain’s immune cells, known as microglia, as central to this side effect. The study also drew parallels between the mechanism behind CAR-T-induced brain fog and that seen in patients after chemotherapy or respiratory infections like flu and COVID-19.
Michelle Monje, professor of pediatric neuro-oncology at Stanford and senior author of the study, emphasized the importance of addressing these cognitive effects:
“CAR-T cell therapy is enormously promising: We are seeing long-term survivors after CAR-T cell therapy for aggressive cancers, saving patients who would otherwise have died. We need to understand all its possible long-term effects, including this newly recognized syndrome of immunotherapy-related cognitive impairment, so we can develop therapeutic approaches to fix it.”
Encouragingly, the research team identified potential strategies to reverse the cognitive impairment in mice. These included temporarily depleting microglia or blocking certain immune signals in the brain, both of which restored normal cognitive function in the animals. The scientists are now investigating how these approaches might be safely adapted for human patients.
While the cognitive symptoms observed are generally mild and do not progress to dementia, they can be frustrating and may persist if not addressed. The findings highlight the need for ongoing research to ensure that life-saving cancer treatments like CAR-T do not compromise patients’ quality of life.
Disclaimer: This article is based on findings from preclinical studies, primarily in animal models. While the results are promising, further research and clinical trials are needed to confirm these effects and potential treatments in humans. Patients should consult their healthcare providers for personalized medical advice.
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