Sustained and specific multiplexed immune checkpoint modulation in CAR T cells induced by targeted epigenome editing

This is the authors' abstract. We don't add key points for this paper.

, both in primary human T cells and in prostate-cancer-specific CAR T cells. Epigenetically modified CAR T cells are indistinguishable from parental cells across a range of functional assays. Although the model does not fully mimic T cell exhaustion, limiting functional assessment, gene silencing remains durable across multiple divisions and repeated CAR stimulations. Furthermore, transcriptomic analysis revealed minimal off-target effects not directly attributable to the effectors used. We demonstrate that targeted epigenome editing is effective and safe for multiplexed gene inhibition and holds potential in engineering CAR T cells with enhanced and customizable features.