{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Can I"],"funding":["Department of Defense grant","NIAID NIH HHS","NCI NIH HHS","Regenerative Medicine Minnesota","NIH HHS"],"pagination":["172"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12150488"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["24(1)"],"pubmed_abstract":["Despite the success of chimeric antigen receptor T (CART) cell therapy in hematological malignancies, durable remissions remain low. Here, we report CART senescence as a potential resistance mechanism in 41BB-costimulated CART cell therapy. To mimic cancer relapse, we utilized an in vitro model with repeated CART cell activation cycles followed by rest periods. Using CD19-targeted CART cells with costimulation via 4-1BB-CD3ζ (BBζ) or CD28-CD3ζ (28ζ), we showed that CART cells undergo functional, phenotypical, and transcriptomic changes of senescence, which is more prominent in BBζ. We then utilized two additional independent strategies to induce senescence through MYC activation and irradiation. Induction of senescence impaired BBζ activity but improved 28ζ activity in preclinical studies."],"journal":["Molecular cancer"],"pubmed_title":["Differential susceptibility and role for senescence in CART cells based on costimulatory domains."],"pmcid":["PMC12150488"],"funding_grant_id":["CA201127","R37CA266344-01","072523 TR 004","R01 CA201127","R37 CA266344","R01 AI179974"],"pubmed_authors":["Yun K","Can I","Kenderian SS","Mai LK","Ekiz HA","Manriquez-Roman C","Sirpilla OL","Ogbodo EJ","Siegler EL","Fonkoua LK","Huynh TN","Xia H","Gutierrez-Ruiz OL","Stewart CM","Sakemura RL","Feigin JM","Rodriguez ML","Hefazi M","Kimball BL","Alkan B","Sezer F","Hamaidi I"],"additional_accession":[]},"is_claimable":false,"name":"Differential susceptibility and role for senescence in CART cells based on costimulatory domains.","description":"Despite the success of chimeric antigen receptor T (CART) cell therapy in hematological malignancies, durable remissions remain low. Here, we report CART senescence as a potential resistance mechanism in 41BB-costimulated CART cell therapy. To mimic cancer relapse, we utilized an in vitro model with repeated CART cell activation cycles followed by rest periods. Using CD19-targeted CART cells with costimulation via 4-1BB-CD3ζ (BBζ) or CD28-CD3ζ (28ζ), we showed that CART cells undergo functional, phenotypical, and transcriptomic changes of senescence, which is more prominent in BBζ. We then utilized two additional independent strategies to induce senescence through MYC activation and irradiation. Induction of senescence impaired BBζ activity but improved 28ζ activity in preclinical studies.","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Jun","modification":"2026-06-03T05:51:55.038Z","creation":"2026-04-25T03:16:24.774Z"},"accession":"S-EPMC12150488","cross_references":{"pubmed":["40495168"],"doi":["10.1186/s12943-025-02371-1"]}}