{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T07:07:07Z","timestamp":1784012827906,"version":"3.55.0"},"reference-count":55,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T00:00:00Z","timestamp":1782172800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T00:00:00Z","timestamp":1782172800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["MedComm"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>KRAS\u2010mutant pancreatic ductal adenocarcinoma (PDAC) exhibits intrinsic resistance to epidermal growth factor receptor (EGFR)\u2010targeted therapies owing to constitutive downstream pathway activation. Nevertheless, IgG1 antibodies may retain therapeutic activity through natural killer (NK) cell\u2010mediated antibody\u2010dependent cellular cytotoxicity (ADCC), thereby bypassing EGFR downstream signaling. However, whether EGFR\u2010targeted IgG1 antibody\u2010mediated ADCC remains effective in KRAS\u2010mutant PDAC, and what determines therapeutic responsiveness, remain unclear. Here, we investigated whether nimotuzumab\u2010mediated ADCC remains effective despite oncogenic KRAS signaling and explored the determinants of its therapeutic efficacy. Using complementary in vitro and in vivo models, including PDAC cell\u2013NK cell co\u2010culture systems, 3D tumor spheroids, and immunodeficient mouse models (subcutaneous and circulating tumor cell\u2010derived xenografts), we demonstrated that combined nimotuzumab and adoptive NK cell therapy exerts potent antitumor efficacy in PDAC. Mechanistically, this treatment drives robust NK cell functional activation (CD107a\/IFN\u2010\u03b3\/TNF\u2010\u03b1), enhances tumor homing, and induces immunogenic cell death. Collectively, our findings demonstrate that KRAS mutations do not compromise nimotuzumab\u2010mediated ADCC, whereas tumor EGFR expression serves as a predictor of therapeutic responsiveness. Ultimately, this study establishes EGFR\u2010directed NK cell immunotherapy as a promising therapeutic strategy for KRAS\u2010mutant PDAC and provides a rationale for integrating targeted antibodies with cellular immunotherapies in other EGFR\u2010expressing malignancies.<\/jats:p>","DOI":"10.1002\/mco2.70860","type":"journal-article","created":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T06:24:25Z","timestamp":1782282265000},"source":"Crossref","is-referenced-by-count":0,"title":["EGFR\u2010Targeting IgG1 Antibody Enhances NK Cell\u2010Mediated Tumor Killing in KRAS\u2010Mutant Pancreatic Cancer"],"prefix":"10.1002","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0801-7005","authenticated-orcid":false,"given":"Ruoxi","family":"Xiao","sequence":"first","affiliation":[{"name":"Shandong Provincial Key Laboratory of Clinical Research for Pancreatic Diseases Tumor Immunology and Cytotherapy Medical Research Center The Affiliated Hospital of Qingdao University  Qingdao China"},{"name":"Department of Clinical Medicine Qingdao University  Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoxiao","family":"Li","sequence":"additional","affiliation":[{"name":"Gastrointestinal Cancer Institute\/Pancreatic Disease Institute The Affiliated Hospital of Qingdao University  Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Li","sequence":"additional","affiliation":[{"name":"Cheeloo College of Medicine Qilu Hospital (Qingdao) Shandong University  Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junjin","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine Qingdao University  Qingdao China"},{"name":"Tumor Immunology and Cytotherapy Medical Research Center The Affiliated Hospital of Qingdao University  Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyuan","family":"Sun","sequence":"additional","affiliation":[{"name":"Gastrointestinal Cancer Institute\/Pancreatic Disease Institute The Affiliated Hospital of Qingdao University  Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenyang","family":"Zhao","sequence":"additional","affiliation":[{"name":"Shandong Provincial Key Laboratory of Clinical Research for Pancreatic Diseases Tumor Immunology and Cytotherapy Medical Research Center The Affiliated Hospital of Qingdao University  Qingdao China"},{"name":"Tumor Immunology and Cytotherapy Medical Research Center The Affiliated Hospital of Qingdao University  Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zimin","family":"Liu","sequence":"additional","affiliation":[{"name":"Gastrointestinal Cancer Institute\/Pancreatic Disease Institute The Affiliated Hospital of Qingdao University  Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruining","family":"Gong","sequence":"additional","affiliation":[{"name":"Shandong Provincial Key Laboratory of Clinical Research for Pancreatic Diseases Tumor Immunology and Cytotherapy Medical Research Center The Affiliated Hospital of Qingdao University  Qingdao China"},{"name":"Gastrointestinal Cancer Institute\/Pancreatic Disease Institute The Affiliated Hospital of Qingdao University  Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minghan","family":"Ren","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine Qingdao University  Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ke","family":"Lei","sequence":"additional","affiliation":[{"name":"Shandong Provincial Key Laboratory of Clinical Research for Pancreatic Diseases Tumor Immunology and Cytotherapy Medical Research Center The Affiliated Hospital of Qingdao University  Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"He","family":"Ren","sequence":"additional","affiliation":[{"name":"Shandong Provincial Key Laboratory of Clinical Research for Pancreatic Diseases Tumor Immunology and Cytotherapy Medical Research Center The Affiliated Hospital of Qingdao University  Qingdao China"},{"name":"Gastrointestinal Cancer Institute\/Pancreatic Disease Institute The Affiliated Hospital of Qingdao University  Qingdao China"},{"name":"Tumor Immunology and Cytotherapy Medical Research Center The Affiliated Hospital of Qingdao University  Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,23]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21871"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI191943"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2021.13027"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/mco2.70162"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2025.217699"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1304369"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2019.1588"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.21.02616"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-18-0123"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2019.10.007"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(21)00136-4"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-024-03362-3"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202203757"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.22.02770"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdx343"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.22.02630"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2009.25.7550"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-37029-3"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2015.03.005"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1155\/2011\/379123"},{"issue":"6","key":"e_1_2_12_22_1","doi-asserted-by":"crossref","first-page":"2595","DOI":"10.1172\/JCI129688","article-title":"Stimulation of Natural Killer Cells With a CD137\u2010Specific Antibody Enhances Trastuzumab Efficacy in Xenotransplant Models of Breast Cancer","volume":"129","author":"Kohrt H. E.","year":"2019","journal-title":"Journal of Clinical Investigation"},{"issue":"3","key":"e_1_2_12_23_1","doi-asserted-by":"crossref","DOI":"10.1136\/jitc-2023-008295","article-title":"Bispecific Immune Cell Engager Enhances the Anticancer Activity of CD16+ NK Cells and Macrophages In Vitro, and Eliminates Cancer Metastasis in NK Humanized NOG Mice","volume":"12","author":"Khoshtinat N. S.","year":"2024","journal-title":"Journal for Immunotherapy of Cancer"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13045-023-01455-z"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2017.00382"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1634\/theoncologist.10-9-760"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41573-019-0052-1"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2023.01.001"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1080\/2162402X.2020.1845424"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41573-022-00413-7"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-023-06945-1"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13045-024-01561-6"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2023.216462"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-025-02129-7"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2010.05.022"},{"key":"e_1_2_12_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature11156"},{"key":"e_1_2_12_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2021.103327"},{"key":"e_1_2_12_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.2012.495"},{"key":"e_1_2_12_39_1","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-11-0269"},{"key":"e_1_2_12_40_1","doi-asserted-by":"publisher","DOI":"10.1158\/2326-6066.CIR-15-0184"},{"key":"e_1_2_12_41_1","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2020-001334"},{"key":"e_1_2_12_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2012.09.014"},{"key":"e_1_2_12_43_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-01-070656"},{"key":"e_1_2_12_44_1","doi-asserted-by":"publisher","DOI":"10.4161\/cbt.11.4.14097"},{"key":"e_1_2_12_45_1","doi-asserted-by":"publisher","DOI":"10.3892\/or.2014.3077"},{"key":"e_1_2_12_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2010.03.005"},{"key":"e_1_2_12_47_1","doi-asserted-by":"publisher","DOI":"10.4161\/onci.26788"},{"key":"e_1_2_12_48_1","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2015.139"},{"key":"e_1_2_12_49_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2015.00543"},{"key":"e_1_2_12_50_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-018-0927-5"},{"key":"e_1_2_12_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mam.2020.100870"},{"key":"e_1_2_12_52_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13062-023-00401-w"},{"key":"e_1_2_12_53_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-12-2426"},{"key":"e_1_2_12_54_1","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2020-000778"},{"key":"e_1_2_12_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2025.217641"},{"key":"e_1_2_12_56_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-07-6768"}],"container-title":["MedComm"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mco2.70860","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/mco2.70860","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mco2.70860","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T06:41:07Z","timestamp":1784011267000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/mco2.70860"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,23]]},"references-count":55,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2026,7]]}},"alternative-id":["10.1002\/mco2.70860"],"URL":"https:\/\/doi.org\/10.1002\/mco2.70860","archive":["Portico"],"relation":{},"ISSN":["2688-2663","2688-2663"],"issn-type":[{"value":"2688-2663","type":"print"},{"value":"2688-2663","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,23]]},"article-number":"e70860"}}