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Epigenetically programmed ‘stem-like’ tissue resident memory CAR T-cells exhibit robust activity against solid and liquid tumors [bulk_ATAC]

ABSTRACT: Chimeric antigen receptor (CAR) T-cells have shown remarkable success in the therapy of hematological malignancies, but they have not yet proven nearly as effective in treating non-hematopoietic cancers. This study proposes augmentation of CAR T-cell function and accumulation in solid tumors by modifying the epigenetic landscape that governs early memory differentiation and adaptation to tissue residency. We identified that a key factor in human tissue-resident memory CAR T-cell (CAR-TRM) formation is activation in the presence of the pleotropic cytokine, TGF-β, which epigenetically enforces a core transcriptional program of both ‘stemness’ and sustained tissue residency. This strategy results in a readily actionable in vitro production method for engineering peripheral blood T-cells into large numbers of ‘stem-like’ CAR-TRM cells resistant to epigenetically-imposed exhaustion that possess enhanced ability to accumulate in situ and rapidly kill cancer cells for more effective immunotherapy.

ORGANISM(S): Homo sapiens

PROVIDER: GSE224862 | GEO | 2023/02/23

REPOSITORIES: GEO

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Epigenetically programmed ‘stem-like’ tissue resident memory CAR T-cells exhibit robust activity against solid and liquid tumors [scRNA]

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Epigenetically programmed ‘stem-like’ tissue resident memory CAR T-cells exhibit robust activity against solid and liquid tumors [bulk_RNA]

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