CAR T therapy affects mouse cognition

Abstract

Many individuals experience cognitive impairment after cancer and cancer treatment. Patients have reported cancer-related cognitive impairment (CRCI) after traditional cancer treatments such as chemotherapy, radiation therapy and surgery, but also after immunotherapy. However, to date, the mechanisms driving CRCI in patients after immunotherapy are unclear. A new study shows that chimeric antigen receptor (CAR) T cell therapy causes cognitive impairment in mouse models of cancer by inducing neuroimmunological changes. In this study, the researchers used patient-derived xenograft murine models of both central nervous system (CNS) and non-CNS cancers, including a model of H3K27M-altered diffuse midline glioma, a pre-B cell acute lymphoblastic leukemia model, two osteosarcoma models and a melanoma model. Behavioral assessment revealed that treatment with CAR T cell therapy (targeting either GD2, CD19, or B7H3 according to tumor type) impaired cognitive performance compared to control mice treated with mock T cells. The treatment also induced neuroinflammation and persistent white matter microglial reactivity, with negative consequences on oligodendrocyte homeostasis and plasticity. These findings could guide the development of therapeutic interventions for patients living with persistent brain fog syndromes after immunotherapy.

Original reference: Geraghty, A.C. et al. Cell https://doi.org/10.1016/j.cell.2025.03.041 (2025)