CAR T cell therapy has revolutionized the way certain types of cancer are treated, and the longer those CAR T cells live in a patient's body, the more effectively they respond to cancer.
FOXO1 is required for memory in T cells and is associated with more durable clinical responses to CAR T cell therapyCAR T cell therapy has revolutionized the way certain types of cancer are treated, and the longer those CAR T cells live in a patient's body, the more effectively they respond to cancer.
To determine what helps CAR T cells live longer, researchers wanted to understand the underlying biology behind memory T cells, which are a type of natural T cell whose purpose is to persist and retain function. One protein of interest, FOXO1, which activates genes associated with T cell memory, has previously been studied in mice but remains under-researched in human T cells or CAR T cells.
Researchers then applied methods to force CAR T cells to overexpress FOXO1, which turned on memory genes and enhanced their ability to persist and fight cancer in animal models. In contrast, when the researchers overexpressed a different memory-promoting factor, there was no improvement in CAR T cell activity, suggesting that FOXO1 plays a more unique role in promoting T cell longevity.
This study was supported by the National Cancer Institute Immunotherapy Discover and Development grants 1U01CA232361-A1, K08CA23188-01, U01CA260852, and U54CA232568-01; the National Human Genome Research Institute grant K99 HGHG012579 ; the Parker Institute for Cancer Immunotherapy; V Foundation for Cancer Research; Society for Immunotherapy of Cancer Rosenberg Scholar Award; Stand Up 2 Cancer -- St. Baldrick's -- NCI grant SU2CAACR-DT1113; and the Virginia and D.K.
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