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- W4306155265 abstract "Chimeric antigen receptor (CAR) T cell therapy has limited efficacy against solid tumors, and one major challenge is T cell exhaustion. To address this challenge, we performed a candidate gene screen using a hypofunction CAR-T cell model and found that depletion of basic leucine zipper ATF-like transcription factor (BATF) improved the antitumor performance of CAR-T cells. In different types of CAR-T cells and mouse OT-1 cells, loss of BATF endows T cells with improved resistance to exhaustion and superior tumor eradication efficacy. Mechanistically, we found that BATF binds to and up-regulates a subset of exhaustion-related genes in human CAR-T cells. BATF regulates the expression of genes involved in development of effector and memory T cells, and knocking out BATF shifts the population toward a more central memory subset. We demonstrate that BATF is a key factor limiting CAR-T cell function and that its depletion enhances the antitumor activity of CAR-T cells against solid tumors." @default.
- W4306155265 created "2022-10-14" @default.
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- W4306155265 date "2022-11-01" @default.
- W4306155265 modified "2023-10-11" @default.
- W4306155265 title "Depletion of BATF in CAR-T cells enhances antitumor activity by inducing resistance against exhaustion and formation of central memory cells" @default.
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- W4306155265 doi "https://doi.org/10.1016/j.ccell.2022.09.013" @default.
- W4306155265 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/36240777" @default.