Deleting DNMT3A in CAR T cells prevents exhaustion and 1 enhances antitumor activity

Whole-genome bisulfite sequencing data generated from WT and DNMT3A KO or IL-10 KO CAR T cells. These data were generate at early (week 1) and later (week 4) time points during in vitro serial stimulation of the CAR T cells, or after infusion into tumor bearing mice. These data document the DNA methylation changes that are coupled to the functional decline in CAR T cells during their sustained stimulation, and the causal nature of DNMT3A-specific methylation in mediating the functional impairment of the CAR T cells. Overall design: Total human T cells were transduced with mock or KO specific guide RNAs complexed with CAS. The gene-edited T cells were then transduce with a vector for expressing a chimeric antigen receptor (CAR). The WT and KO CAR T cells were then cultured in the presence of tumor cells that express the cognate antigen to stimulate the CAR-T cells. DNA was extracted from the stimulated CAR T cells at the specified time points and subjected to whole-genome bisulfite sequencing.