{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Aznar MA"],"funding":["Parker Institute for Cancer Immunotherapy","Stand up to Cancer","National Cancer Institute","National Institutes of Health","American Cancer Society Inc"],"pagination":["102301"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12490220"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["6(9)"],"pubmed_abstract":["Patients with advanced pancreatic ductal adenocarcinoma (PDAC) have a median survival of less than a year, highlighting the urgent need for treatment advancements. We report on a phase 1 clinical trial assessing the safety and feasibility of intravenous and local administration of anti-mesothelin CAR T cells in patients with advanced PDAC. While therapy is well tolerated, it demonstrates limited clinical efficacy. Analyses of patient samples provide insights into mechanisms of treatment resistance. Single-cell genomic approaches reveal that post-infusion CAR T cells express exhaustion signatures, including previously identified transcription factors ID3 and SOX4, and display enrichment for a GZMK<sup>+</sup> phenotype. Single knockout of ID3 or SOX4 enhances efficacy in xenograft models, t"],"journal":["Cell reports. Medicine"],"pubmed_title":["Clinical and molecular dissection of CAR T cell resistance in pancreatic cancer."],"pmcid":["PMC12490220"],"funding_grant_id":["SU2C-RT6162","P30 CA016520","PF-19-202-01-DMC","S10 OD023465-01A1","R50CA305050","SU2C-AACR-DT21-17","CA263922"],"pubmed_authors":["Dowd E","Nadolski G","Rennels AK","Agarwal S","Wilson W","Huang H","Haas A","Hwang WT","Gonzalez VE","Torigian DA","June CH","Barber-Rotenberg JS","Good CR","Berger SL","O'Hara MH","Tanyi J","Young RM","Aznar MA","Rech AJ","Siegel DL","Glastad KM","Hexner EO","Donahue G","Brennan A","Zhang Z","Jadlowsky JK","Watts A","Gonzales D","Fraietta JA","Alexander KA","Plesa G","Kuramitsu S"],"additional_accession":[]},"is_claimable":false,"name":"Clinical and molecular dissection of CAR T cell resistance in pancreatic cancer.","description":"Patients with advanced pancreatic ductal adenocarcinoma (PDAC) have a median survival of less than a year, highlighting the urgent need for treatment advancements. We report on a phase 1 clinical trial assessing the safety and feasibility of intravenous and local administration of anti-mesothelin CAR T cells in patients with advanced PDAC. While therapy is well tolerated, it demonstrates limited clinical efficacy. Analyses of patient samples provide insights into mechanisms of treatment resistance. Single-cell genomic approaches reveal that post-infusion CAR T cells express exhaustion signatures, including previously identified transcription factors ID3 and SOX4, and display enrichment for a GZMK<sup>+</sup> phenotype. Single knockout of ID3 or SOX4 enhances efficacy in xenograft models, t","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Sep","modification":"2026-07-15T06:49:53.679Z","creation":"2026-06-30T03:22:46.844Z"},"accession":"S-EPMC12490220","cross_references":{"pubmed":["40829595"],"doi":["10.1016/j.xcrm.2025.102301"]}}