articleNatureApr 10, 2024HYBRID OA

FOXO1 enhances CAR T cell stemness, metabolic fitness and efficacy

The University of Melbourne · Peter MacCallum Cancer Centre · +4 more institutions

PubMed
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Abstract

Abstract Chimeric antigen receptor (CAR) T cell therapy has transformed the treatment of haematological malignancies such as acute lymphoblastic leukaemia, B cell lymphoma and multiple myeloma 1–4 , but the efficacy of CAR T cell therapy in solid tumours has been limited 5 . This is owing to a number of factors, including the immunosuppressive tumour microenvironment that gives rise to poorly persisting and metabolically dysfunctional T cells. Analysis of anti-CD19 CAR T cells used clinically has shown that positive treatment outcomes are associated with a more ‘stem-like’ phenotype and increased mitochondrial mass 6–8 . We therefore sought to identify transcription factors that could enhance CAR T cell…

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