{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Prinzing B"],"funding":["NIAID NIH HHS","NINDS NIH HHS","NCI NIH HHS"],"pagination":["eabh0272"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC8733956"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["13(620)"],"pubmed_abstract":["Chimeric antigen receptor (CAR) T cell therapy is revolutionizing cancer immunotherapy for patients with B cell malignancies and is now being developed for solid tumors and chronic viral infections. Although clinical trials have demonstrated the curative potential of CAR T cell therapy, a substantial and well-established limitation is the heightened contraction and transient persistence of CAR T cells during prolonged antigen exposure. The underlying mechanism(s) for this dysfunctional state, often termed CAR T cell exhaustion, remains poorly defined. Here, we report that exhaustion of human CAR T cells occurs through an epigenetic repression of the T cell’s multipotent developmental potential. Deletion of the de novo DNA methyltransferase 3 alpha (DNMT3A) in T cells expressing first- or s"],"journal":["Science translational medicine"],"pubmed_title":["Deleting DNMT3A in CAR T cells prevents exhaustion and enhances antitumor activity."],"pmcid":["PMC8733956"],"funding_grant_id":["R01 NS106379","R00 CA256262","P30 CA021765","R01 AI114442","R01 NS121249","F31 CA250401","R01 CA173750","K99 CA256262","R01 CA237311","R50 CA211481","U01 AI157189"],"pubmed_authors":["Yi Z","Langfitt DM","Haydar D","Zebley CC","Brown C","Pruett-Miller SM","Tsai SQ","Vogel P","Crawford JC","Youngblood B","Anido AA","Fan Y","Krenciute G","Park JJ","Zhou S","Gottschalk S","Nguyen P","Lazzarotto CR","Petersen CT","Boi SK","Prinzing B","Bell M","DeRenzo C","Alli S","Riberdy JM","Velasquez MP","Houke H"],"additional_accession":[]},"is_claimable":false,"name":"Deleting DNMT3A in CAR T cells prevents exhaustion and enhances antitumor activity.","description":"Chimeric antigen receptor (CAR) T cell therapy is revolutionizing cancer immunotherapy for patients with B cell malignancies and is now being developed for solid tumors and chronic viral infections. Although clinical trials have demonstrated the curative potential of CAR T cell therapy, a substantial and well-established limitation is the heightened contraction and transient persistence of CAR T cells during prolonged antigen exposure. The underlying mechanism(s) for this dysfunctional state, often termed CAR T cell exhaustion, remains poorly defined. Here, we report that exhaustion of human CAR T cells occurs through an epigenetic repression of the T cell’s multipotent developmental potential. Deletion of the de novo DNA methyltransferase 3 alpha (DNMT3A) in T cells expressing first- or s","dates":{"release":"2021-01-01T00:00:00Z","publication":"2021 Nov","modification":"2025-04-26T13:03:24.581Z","creation":"2025-02-19T04:07:26.205Z"},"accession":"S-EPMC8733956","cross_references":{"pubmed":["34788079"],"doi":["10.1126/scitranslmed.abh0272"]}}