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This study explores chimeric-antigen receptor (CAR)–based adoptive immunotherapy for cervical cancer, which remains largely underinvestigated. Using alpharetroviral SIN vectors, natural killer (NK) cells were engineered with a third-generation Mesothelin CAR (CD28 and 4-1BB costimulatory domains). Anti-Mesothelin CAR-NK cells showed strong cytotoxicity against cervical cancer cells in 2D and 3D models, with increased degranulation upon Mesothelin+ target exposure. CRISPR-Cas9 generated Mesothelin− cervical cancer cells to confirm antigen specificity. Combined CAR-NK-92 treatment with chemotherapy enhanced cancer-cell elimination versus monotherapy, supporting anti-Mesothelin CAR-NK cells as a promising therapeutic option for cervical cancer and other Mesothelin+ malignancies.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":40,"@type":76,"position":81},"https://docshare.wps.com/document/research-report/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/anti-mesothelin-car-nk-cells-as-a-novel-targeted-therapy-against-cervical-cancer/332932/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/anti-mesothelin-car-nk-cells-as-a-novel-targeted-therapy-against-cervical-cancer/332932.png","ImageObject",300,407,{"name":92,"@type":93},"Theodora","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-23","2026-09-21",true,{"@type":102,"interactionType":103,"userInteractionCount":52},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"Why is new targeted therapy needed for advanced cervical cancer?","Question",{"text":112,"@type":113},"Current outcomes are poor largely because patients often develop resistance to existing treatment paradigms. Targeted therapy approaches are needed to improve therapeutic effectiveness.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How were CAR-NK cells engineered in this study?",{"text":117,"@type":113},"Alpharetroviral SIN vectors were used to equip NK cells with a third-generation CAR targeting Mesothelin, including CD28 and 4-1BB costimulatory domains.",{"name":119,"@type":110,"acceptedAnswer":120},"What evidence supports the effectiveness and specificity of anti-Mesothelin CAR-NK cells?",{"text":121,"@type":113},"Anti-Mesothelin CAR-NK cells showed high cytotoxicity against cervical cancer cells in 2D and 3D models and increased degranulation upon exposure to Mesothelin+ targets. Antigen specificity was demonstrated using CRISPR-Cas9 Mesothelin knockout cervical cancer cells.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},332932,1790156941,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":39,"category_name":40,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":52,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":56,"language":139,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":140,"faqs":141,"seo_title":142,"seo_description":67,"update_tm":143,"read_time":144,"preview_page_count":4},687197207919,"https://ap-avatar.wpscdn.com/avatar/a000253d6f5f7c60be?x-image-process=image/resize,m_fixed,w_180,h_180&k=1779446848396160552","TYPE Original Research PUBLISHED 16 December 2024 DOI 10.3389/fimmu.2024.1485461  \nOPEN ACCESS  \nEDITED BY  \nCyrille J. Cohen,  \nBar-Ilan University, Israel  \nREVIEWED BY  \nYunlong Zhao,  \nSt. Jude Children ’s Research Hospital, United States  \nAndreas A. Hombach,  \nUniversity of Cologne, Germany  \n*CORRESPONDENCE  \nRüdiger Klapdor  \n [Klapdor.Ruediger@mh-hannover.de](Klapdor.Ruediger@mh-hannover.de);  \n [Ruediger.Klapdor@immanuelalbertinen.de](Ruediger.Klapdor@immanuelalbertinen.de)[ ](Ruediger.Klapdor@immanuelalbertinen.de)Michael Alexander Morgan  \n [Morgan.Michael@mh-hannover.de](Morgan.Michael@mh-hannover.de)[ ](Morgan.Michael@mh-hannover.de)Axel Schambach  \n [Schambach.Axel@mh-hannover.de](Schambach.Axel@mh-hannover.de)  \n†These authors have contributed equally to this work and share first authorship  \n‡These authors share senior authorship  \nRECEIVED 23 August 2024  \nACCEPTED 18 November 2024  \nPUBLISHED 16 December 2024  \nCITATION  \nKutle I, Polten R, Stalp JL, Hachenberg J, Todzey F, Hass R, Zimmermann K,  \nvon der Ohe J, von Kaisenberg C, Neubert L, Kamp JC, Schaudien D, Seyda A-K, Hillemanns P, Klapdor R, Morgan MA and  \nSchambach A (2024) Anti-Mesothelin CAR-NK cells as a novel targeted therapy against cervical cancer.  \nFront. Immunol. 15:1485461 .  \ndoi: 10.3389/fimmu.2024.1485461  \nCOPYRIGHT  \n© 2024 Kutle, Polten, Stalp, Hachenberg, Todzey, Hass, Zimmermann, von der Ohe, von Kaisenberg, Neubert, Kamp, Schaudien, Seyda, Hillemanns, Klapdor, Morgan and Schambach. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.  \nAnti-Mesothelin CAR-NK cells as a novel targeted therapy against cervical cancer  \nIvana Kutle 1†, Robert Polten 1†, Jan Lennart Stalp 1,2, Jens Hachenberg 1,2, Felix Todzey1, Ralf Hass 2, Katharina Zimmermann 1, Juliane von der Ohe 2,  \nConstantin von Kaisenberg 2, Lavinia Neubert 3,4, Jan C. Kamp 4,5, Dirk Schaudien6, Ann-Kathrin Seyda 1, Peter Hillemanns 2, Rüdiger Klapdor 1,2,7*‡, Michael Alexander Morgan 1*‡  \nand Axel Schambach 1,8*‡  \n1 Institute of Experimental Hematology, Hannover Medical School, Hannover, Germany, 2 Department of Gynecology and Obstetrics, Hannover Medical School, Hannover, Germany, 3 Institute of Pathology, Hannover Medical School, Hannover, Germany, 4 Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), German Center for Lung Research (DZL),  \nHannover, Germany, 5 Department of Respiratory Medicine and Infectious Diseases, Hannover Medical School, Hannover, Germany, 6 Fraunhofer Institute for Toxicology and Experimental Medicine, ITEM, Hannover, Germany, 7 Department of Gynecology and Obstetrics, Albertinen Hospital Hamburg, Hamburg, Germany, 8 Division of Hematology/Oncology, Boston Children ’s Hospital, Harvard Medical School, Boston, MA, United States  \nResistance to the currently available treatment paradigms is one of the main factors that contributes to poor outcomes in patients with advanced cervical cancer. Novel targeted therapy approaches might enhance the patient’s treatment outcome and are urgently needed for this malignancy. While chimeric-antigen receptor (CAR)-based adoptive immunotherapy displays a promising treatment strategy for liquid cancers, their use against cervical cancer is largely unexplored. This study used alpharetroviral SIN vectors to equip natural killer (NK) cells with a third-generation CAR (including CD28 and 4-1BB co-stimulatory domains) targeting Mesothelin, which was identified to be highly expressed on primary human cervical cancer tissues and cervical cancer cell lines in this and other studies. Anti-Mesothelin CAR-NK c","cbCaihfEudyaNWLf","https://ap.wps.com/l/cbCaihfEudyaNWLf","pdf",12364416,"English","# Introduction\n## Targeted therapy and CAR-based cell therapy background\n# Results\n## CAR-NK engineering with Mesothelin targeting\n## Cytotoxicity in 2D and 3D culture models\n## Antigen specificity using Mesothelin knockout cells\n## Combination with chemotherapy\n# Discussion\n## Therapeutic promise of anti-Mesothelin CAR-NK cells","[{\"question\":\"Why is new targeted therapy needed for advanced cervical cancer?\",\"answer\":\"Current outcomes are poor largely because patients often develop resistance to existing treatment paradigms. Targeted therapy approaches are needed to improve therapeutic effectiveness.\"},{\"question\":\"How were CAR-NK cells engineered in this study?\",\"answer\":\"Alpharetroviral SIN vectors were used to equip NK cells with a third-generation CAR targeting Mesothelin, including CD28 and 4-1BB costimulatory domains.\"},{\"question\":\"What evidence supports the effectiveness and specificity of anti-Mesothelin CAR-NK cells?\",\"answer\":\"Anti-Mesothelin CAR-NK cells showed high cytotoxicity against cervical cancer cells in 2D and 3D models and increased degranulation upon exposure to Mesothelin+ targets. Antigen specificity was demonstrated using CRISPR-Cas9 Mesothelin knockout cervical cancer cells.\"}]","Anti-Mesothelin CAR-NK cells as a novel targeted therapy against cervical cancer | PDF",1790000054,48]