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Recent advances in chimeric antigen receptor (CAR)-T cell immunotherapy have offered renewed hope. The pivotal factors determining the effectiveness of CAR-T cells in the clinic is the selection of a reliable target and a specific ectodomain of CAR molecule. EpCAM is widely expressed in epithelial tumors, including pancreatic cancer, and is used as a tumor target in clinical trials of CAR-T cell therapy for gastric and colorectal cancers. However, the feasibility of using EpCAM CAR-T cells in pancreatic cancer still needs to be verified. In this work, we reported novel EpCAM CAR-T cells with a fully human single-chain variable fragment and evaluated their cytotoxic effects in a panel of pancreatic adenocarcinoma cell lines, three-dimensional tumor spheroid models and patient-derived organoids, and two xenograft mouse models. We demonstrated that EpCAM CAR-T cells exhibited potent and specific anti-tumor activity against EpCAM positive pancreatic cancer in vitro and in vivo, without adverse effects by systematic delivery in xenograft mouse models. Our preclinical results provided evidence of the efficacy and feasibility of EpCAM CAR-T cells for the immunotherapy of pancreatic cancer.<\/jats:p>","DOI":"10.1007\/s00262-025-04267-x","type":"journal-article","created":{"date-parts":[[2025,12,19]],"date-time":"2025-12-19T06:21:45Z","timestamp":1766125305000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Preclinical evaluation of CAR-T cell immunotherapy with a fully human EpCAM-specific scFv against pancreatic cancer"],"prefix":"10.1007","volume":"75","author":[{"given":"Ying-Ying","family":"Fan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ya-Ling","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Fan","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Si-Qi","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao-Ran","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Wei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian-Rong","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,12,19]]},"reference":[{"issue":"3","key":"4267_CR1","doi-asserted-by":"publisher","first-page":"1026","DOI":"10.1007\/s12029-024-01078-8","volume":"55","author":"Z Sarfraz","year":"2024","unstructured":"Sarfraz Z, Sarfraz A, Farooq MD et al (2024) The current landscape of clinical trials for immunotherapy in pancreatic cancer: a state-of-the-art review. 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H., YY. F., YL. L., XF. L., H. Y., and HR. Z. are employees of National Vaccine and Serum Institute. The authors declare no conflicts of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"Samples from patients were collected after informed consent, in accordance with the guidelines established by the Ethical Committees of the Yixing People\u2019s Hospital (2020-060). The animal study was approved by IACUC of the National Vaccine and Serum Institute (NVSI) (No. NVSI\u2013RCD\u2013JSDW\u2013ER-2024158, No. NVSI\u2013RCD\u2013JSDW\u2013ER-2024375).","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}}],"article-number":"22"}}