While CAR-T cell therapy has shown promise in treating cancer, it may also lead to "brain fog" or forgetfulness and difficulty concentrating, according to a study. CAR-T cell therapy is immunotherapy where a patient's immune cells – T cells -- are genetically engineered and infused into the bloodstream to recognise and destroy cancer cells more effectively.
The study led by a team from Stanford University showed that CAR-T cell therapy causes mild cognitive impairments, independent of other cancer treatments.Notably, this happens via the same cellular mechanism as cognitive impairment from two other causes: chemotherapy and respiratory infections such as flu and Covid-19.
"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," said Michelle Monje, Professor in Pediatric Neuro-Oncology at the Stanford Medicine.
"We need to understand all its possible long-term effects, including this newly recognised syndrome of immunotherapy-related cognitive impairment, so we can develop therapeutic approaches to fix it," Monje added.In the paper published in the journal Cell, the research team studied mice that had tumours induced in the brain, blood, skin, and bone.
They wanted to understand the influence on cognition of CAR-T cell treatment in combination with the tumours' location (originating in, spreading to, or staying outside the brain), as well as the degree to which the engineered cells evoked additional, accompanying immune responses.
Before and after CAR-T cell treatment, the researchers used standard cognitive tests on the mice, measuring how mice responded to a novel object and navigated a simple maze.CAR-T therapy caused mild cognitive impairment in mice with cancers originating in, metastasising to, and located completely outside the brain.
The only mice tested that did not develop cognitive impairment after CAR-T treatment were those that had bone cancer that causes minimal additional inflammation beyond the cancer-fighting activity of the CAR-T cells.The researchers demonstrated that the brain's immune cells, called microglia, are key players in the problem.
The study also identified strategies for reversing the problem.Medications that ameliorate brain fog will enable better recovery from cancer immunotherapies, the researchers said.