ArticleCell reports. Medicine2025
Clinical and molecular dissection of CAR T cell resistance in pancreatic cancer.
Abstract readClinical Trial, Phase I
In one paragraph
Article in Cell reports. Medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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22citing papers in PubMed
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Who cites it
22 citing papers in PubMed.
- Biomarker-Driven Strategies for Stromal Reprogramming in Pancreatic Ductal Adenocarcinoma.Cells · 2026Review
- Challenges and opportunities in combining radiotherapy and immunotherapy for localized pancreatic cancer.Nature reviews. Gastroenterology & hepatology · 2026Review
- Advances, challenges, and innovative strategies of CAR-T cell therapy in pancreatic cancer.Biomarker research · 2026Review
- Quiescent tumor cells shape the immunosuppressive microenvironment in pancreatic cancer.Nature communications · 2026Article
- Review
- The interplay between p21-activated kinases and tumour-infiltrating dendritic cells and T cells and its implication in pancreatic cancer immunotherapy.Cell communication and signaling : CCS · 2026Review
- Co-editing of NKG2A and FAS increases long-term cytotoxic capacity and persistence of CAR NK cells.Molecular therapy. Oncology · 2026Article
- Molecular subtypes in pancreatic cancer: from academic promise to clinical reality.Molecular cancer · 2026Review
- Cell-derived Nanoparticles Provide a Robust Platform to Manufacture Therapeutic T cells.Research square · 2026Article
- Ibrutinib and PD-1 Blockade Potentiate Mesothelin-Targeting CAR T-cell Therapy in Preclinical Models of Pancreatic Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Article
- Adoptive cell therapies in solid tumors: current clinical landscape, challenges, and future directions.Frontiers in immunology · 2026Review
- The life cycle of tertiary lymphoid structures in pancreatic cancer-a window of opportunity for immunotherapy.Frontiers in immunology · 2026Review
- Evaluating mesothelin as an immunotherapeutic target for endogenous T cells.Frontiers in immunology · 2026Article
- Erythrocyte membrane-liposome coating sustains circulation stability and targeted tumor therapy of CAR-T cells.Frontiers in immunology · 2026Article
- Interleukin 6 Drives Durable T Cell-Mediated Immunity to Pancreatic Cancer.Cellular and molecular gastroenterology and hepatology · 2026Article
- CAR-T cell therapy for pancreatic cancer: Translating emerging targets and dual-targeting strategies from solid tumors.Frontiers in immunology · 2026Review
- CAR T cell cancer immunotherapy: who does the job?Frontiers in immunology · 2026Review
- Antigen-experienced NK-T cells: integrating new insights and exploring therapeutic potential in cancer immunotherapy.Frontiers in immunology · 2026Review
- Emerging Chimeric Antigen Receptor-Immune Cell Therapy for Pancreatic Cancer: Mechanisms, Clinical Advances, and Future Perspectives.Oncology research · 2026Review
- Interleukin 6 drives durable T cell-mediated immunity to pancreatic cancer.bioRxiv : the preprint server for biology · 2025Article
Corrections and comments
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Authors and funding
32 authors.
M Angela AznarCenter for Cellular Immunotherapies, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA; Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
Charly R GoodDepartment of Cell and Developmental Biology, Penn Epigenetics Institute, Perelman School of Medicine, Philadelphia, PA 19104, USA.
Julie S Barber-RotenbergCenter for Cellular Immunotherapies, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
Sangya AgarwalCenter for Cellular Immunotherapies, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
Wesley WilsonCenter for Cellular Immunotherapies, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
Alex WattsDepartment of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Zhen ZhangDepartment of Cell and Developmental Biology, Penn Epigenetics Institute, Perelman School of Medicine, Philadelphia, PA 19104, USA.
Donna GonzalesCenter for Cellular Immunotherapies, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
Greg DonahueDepartment of Cell and Developmental Biology, Penn Epigenetics Institute, Perelman School of Medicine, Philadelphia, PA 19104, USA.
Wei-Ting HwangDepartment of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Austin K RennelsCenter for Cellular Immunotherapies, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
Andrew J RechCenter for Cellular Immunotherapies, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
Shunichiro KuramitsuCenter for Cellular Immunotherapies, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
Hua HuangDepartment of Cell and Developmental Biology, Penn Epigenetics Institute, Perelman School of Medicine, Philadelphia, PA 19104, USA; Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA; Institute for Immunology and Immune Health, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
Karl M GlastadDepartment of Cell and Developmental Biology, Penn Epigenetics Institute, Perelman School of Medicine, Philadelphia, PA 19104, USA.
Katherine A AlexanderDepartment of Cell and Developmental Biology, Penn Epigenetics Institute, Perelman School of Medicine, Philadelphia, PA 19104, USA.
Gabriela PlesaCenter for Cellular Immunotherapies, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
Emily DowdCenter for Cellular Immunotherapies, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
Andrea BrennanCenter for Cellular Immunotherapies, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
Donald L SiegelCenter for Cellular Immunotherapies, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA; Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
Janos TanyiAbramson Cancer Center, University of Pennsylvania, Philadelphia, PA 19104, USA; Ovarian Cancer Research Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Andrew HaasAbramson Cancer Center, University of Pennsylvania, Philadelphia, PA 19104, USA; Division of Pulmonary, Allergy, and Critical Care, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Drew A TorigianAbramson Cancer Center, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Gregory NadolskiAbramson Cancer Center, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Vanessa E GonzalezCenter for Cellular Immunotherapies, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
Elizabeth O HexnerCenter for Cellular Immunotherapies, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA; Division of Hematology/Oncology, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
Joseph A FraiettaCenter for Cellular Immunotherapies, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA; Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA; Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Julie K JadlowskyCenter for Cellular Immunotherapies, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
Regina M YoungCenter for Cellular Immunotherapies, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA; Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA; Parker Institute for Cancer Immunotherapy, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: ryoung@upenn.edu.
Shelley L BergerDepartment of Cell and Developmental Biology, Penn Epigenetics Institute, Perelman School of Medicine, Philadelphia, PA 19104, USA. Electronic address: bergers@pennmedicine.upenn.edu.
Carl H JuneCenter for Cellular Immunotherapies, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA; Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA; Parker Institute for Cancer Immunotherapy, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: cjune@upenn.edu.
Mark H O'HaraAbramson Cancer Center, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Medicine, Division of Hematology and Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: mark.ohara@pennmedicine.upenn.edu.
Funding
Interaction between nuclear epigenetic and metabolic pathways in cancerR35CA263922 · NCI · UNIVERSITY OF PENNSYLVANIA · PI SHELLEY L BERGER · 2022 to 2026
$4.8MResponse and resistance to chimeric antigen receptor T cell therapy in human solid tumors using spatial multi-omicsDP5OD037346 · OD · UNIVERSITY OF PENNSYLVANIA · PI Andrew John Rech · 2024 to 2026
$1.2MMechanisms of gene regulation in cancerR50CA305050 · NCI · UNIVERSITY OF PENNSYLVANIA · PI Charly Ryan Good · 2025 to 2026
$460kNCI NIH HHS R35 CA263922NCI NIH HHS R50 CA305050NIH HHS DP5 OD037346
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
Indexed as
Carcinoma, Pancreatic DuctalImmunotherapy, AdoptivePancreatic NeoplasmsReceptors, Chimeric AntigenT-LymphocytesAgedAnimalsFeasibility StudiesFemaleGPI-Linked ProteinsHumansInhibitor of Differentiation ProteinsMaleMesothelinMiceMiddle AgedGPI-Linked ProteinsInhibitor of Differentiation ProteinsMesothelinReceptors, Chimeric AntigenSOX4 protein, humanSOXC Transcription FactorscancerCAR T cellsclinical trialID3immunotherapypancreatic cancersingle-cell RNA-seqSOX4T cell dysfunctionT cell exhaustion
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