[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"doc-seo-450820-105":3,"detail-sidebar-cat-0-en-105":81,"doc-detail-450820-en":130},{"code":4,"msg":5,"data":6},0,"ok",{"site_id":7,"language":8,"slug":9,"title":10,"keywords":11,"description":12,"schema_data":13,"social_meta":74,"head_meta":76,"extra_data":78,"updated_unix":80},105,"en","met-enhances-amivantamab-binding-to-egfr-and-antibody-dependent-cellular-toxicity-cancer-science-original-article","MET Enhances Amivantamab Binding to EGFR and Antibody-Dependent Cellular Toxicity - Cancer Science Original Article","","Amivantamab, a bispecific antibody targeting EGFR and MET, was investigated to clarify how MET influences EGFR binding and amivantamab-induced antibody-dependent cellular toxicity (ADCC). Real-time HS-AFM imaging showed direct binding to EGFR- and MET-extracellular domains and visualization of EGFR–MET trimer formation. Western blot of gel filtration fractions demonstrated that MET-ECD enhances amivantamab binding to EGFR-ECD and promotes trimer formation. In NSCLC cells with common EGFR mutations, MET increased mononuclear cell-mediated ADCC activity, especially at low amivantamab concentrations, correlating ADCC with EGFR expression and supporting improved efficacy.",{"@graph":14,"@context":73},[15,34,56],{"@type":16,"itemListElement":17},"BreadcrumbList",[18,23,27,31],{"item":19,"name":20,"@type":21,"position":22},"https://docshare.wps.com","Home","ListItem",1,{"item":24,"name":25,"@type":21,"position":26},"https://docshare.wps.com/document/","Document",2,{"item":28,"name":29,"@type":21,"position":30},"https://docshare.wps.com/document/healthcare/","Healthcare",3,{"item":32,"name":10,"@type":21,"position":33},"https://docshare.wps.com/document/met-enhances-amivantamab-binding-to-egfr-and-antibody-dependent-cellular-toxicity-cancer-science-original-article/450820/",4,{"url":32,"name":10,"@type":35,"image":36,"author":41,"headline":10,"publisher":44,"fileFormat":47,"inLanguage":8,"description":12,"dateModified":48,"datePublished":49,"encodingFormat":47,"isAccessibleForFree":50,"interactionStatistic":51},"DigitalDocument",{"url":37,"@type":38,"width":39,"height":40},"https://docshare.wps.com/thumbnails/met-enhances-amivantamab-binding-to-egfr-and-antibody-dependent-cellular-toxicity-cancer-science-original-article/450820.png","ImageObject",300,407,{"name":42,"@type":43},"Sarah ","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-10-28","2026-09-30",true,{"@type":52,"interactionType":53,"userInteractionCount":55},"InteractionCounter",{"@type":54},"ViewAction",5,{"@type":57,"mainEntity":58},"FAQPage",[59,65,69],{"name":60,"@type":61,"acceptedAnswer":62},"What question does the study address about MET and amivantamab?","Question",{"text":63,"@type":64},"The study examines whether MET contributes to amivantamab’s binding to EGFR and whether this affects amivantamab-induced ADCC.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"How did the researchers observe amivantamab binding to EGFR and MET?",{"text":68,"@type":64},"They used high-speed atomic force microscopy (HS-AFM) to visualize real-time binding to EGFR-ECD and MET-ECD and to visualize binding involving EGFR domain 3 and the MET Sema domain.",{"name":70,"@type":61,"acceptedAnswer":71},"What role does MET play in ADCC activity and under what amivantamab conditions?",{"text":72,"@type":64},"MET enhances mononuclear cell-mediated ADCC in NSCLC with common EGFR mutations, with stronger enhancement observed at low concentrations of amivantamab; ADCC activity also correlates with EGFR expression in tumor cells.","https://schema.org",{"og:url":32,"og:type":75,"og:title":10,"og:site_name":45,"og:description":12},"article",{"robots":77,"canonical":32},"index,follow",{"doc_id":79,"site_id":7},450820,1792666210,{"code":4,"msg":82,"data":83},"success",[84,88,92,96,100,105,109,114,119,122,126],{"id":22,"doc_module":4,"doc_module_name":25,"category_name":85,"show_sort_weight":86,"slug":87},"Story & Novel",90,"story-novel",{"id":26,"doc_module":4,"doc_module_name":25,"category_name":89,"show_sort_weight":90,"slug":91},"Literature",80,"literature",{"id":33,"doc_module":4,"doc_module_name":25,"category_name":93,"show_sort_weight":94,"slug":95},"Exam",70,"exam",{"id":55,"doc_module":4,"doc_module_name":25,"category_name":97,"show_sort_weight":98,"slug":99},"Comic",60,"comic",{"id":101,"doc_module":4,"doc_module_name":25,"category_name":102,"show_sort_weight":103,"slug":104},6,"Technology",50,"technology",{"id":106,"doc_module":4,"doc_module_name":25,"category_name":29,"show_sort_weight":107,"slug":108},7,40,"healthcare",{"id":110,"doc_module":4,"doc_module_name":25,"category_name":111,"show_sort_weight":112,"slug":113},8,"Research & Report",30,"research-report",{"id":115,"doc_module":4,"doc_module_name":25,"category_name":116,"show_sort_weight":117,"slug":118},9,"Religion & Spirituality",20,"religion-spirituality",{"id":117,"doc_module":4,"doc_module_name":25,"category_name":120,"show_sort_weight":117,"slug":121},"World Cup","world-cup",{"id":123,"doc_module":4,"doc_module_name":25,"category_name":124,"show_sort_weight":123,"slug":125},10,"Lifestyle","lifestyle",{"id":127,"doc_module":4,"doc_module_name":25,"category_name":128,"show_sort_weight":55,"slug":129},19,"General","general",{"code":4,"msg":82,"data":131},{"doc_id":79,"user_id":132,"nickname":42,"user_avatar":133,"doc_module":4,"category_id":106,"category_name":29,"doc_title":10,"doc_description":12,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":55,"is_deleted":4,"is_public":22,"is_downloadable":22,"audit_status":22,"page_count":139,"language":140,"language_code":8,"site_id":7,"html_lang":8,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":12,"update_tm":144,"read_time":112,"preview_page_count":4},962085320529,"https://ap-avatar.wpscdn.com/davatar_9964176cb1d06d4a9deccf72a44ae3dc","Cancer Science  \nORIGINAL ARTICLE  OPEN ACCESS   \nMET Enhances Amivantamab Binding to EGFR and Antibody-Dependent Cellular Toxicity  \nShigeki Sato1,2  | Neval Yilmaz3 | Sachiko Arai3 | Katsuya Sakai3,4 | Hiroki Sato4 | Yuya Murase5  | Tsukasa Ueda5 | Hayato Koba5 | Shigeki Nanjo1,5 | Yuichi Tambo5 | Hiroshi Kotani1,2  | Koji Fukuda1,2,3  |  \nHiroaki Taniguchi2 | Romain Amyot3 | Holger Flechsig3 | Hideko Isozaki6 | Kunio Matsumoto3,4  | Seiji Yano1,3,5   \n1Department of Medical Oncology, Cancer Research Institute, Kanazawa University, Kanazawa, Japan | 2Division of Innovative Cancer Control Research, Cancer Research Institute, Kanazawa University, Kanazawa, Japan | 3Nano Life Science Institute, Kanazawa University, Kanazawa, Japan | 4Division of Tumor Dynamics and Regulation, Cancer Research Institute, Kanazawa University, Kanazawa, Japan | 5Department of Respiratory Medicine, Faculty of Medicine, Institute of Medical, Pharmaceutical, and Health Sciences, Kanazawa University, Kanazawa, Japan | 6Division of Genome Biology, Cancer  \nResearch Institute, Kanazawa University, Kanazawa, Japan Correspondence: Seiji Yano ([syano@staff.kanazawa-u.ac.jp](syano@staff.kanazawa-u.ac.jp))  \nReceived: 31 July 2025 | Revised: 30 September 2025 | Accepted: 6 October 2025  \nFunding: This study was supported by the grant from Janssen Pharma and from JSPS KAKENHI [grant numbers 23K27609 (Seiji Yano)] .  \nKeywords: AFM | Amivantamab | bispecific antibody | EGFR | MET  \nABSTRACT  \nAmivantamab is a bispecific antibody against epidermal growth factor receptor (EGFR) and MET that has been approved for nonsmall cell lung cancer (NSCLC) with EGFR exon 20 insertion mutations and common EGFR mutations, such as exon 19 deletion and L858R. MET has attracted attention as a therapeutic target for lung cancer; however, its role in EGFR binding and amivantamab-induced antibody-dependent cellular toxicity (ADCC) remains unclear. We used high-speed atomic force microscopy (HS-AFM) to observe the real-time binding of amivantamab to the EGFR-extracellular domain (ECD) and MET-ECD and visualized the binding of amivantamab to the EGFR domain 3 and MET Sema domain. Furthermore, we observed the trimer comprising amivantamab bound to EGFR and MET. Western blot analysis of the gel filtration fractions revealed that the METECD enhanced the binding of amivantamab to the EGFR-ECD, which promoted trimer formation. Moreover, amivantamabinduced mononuclear cell-mediated ADCC in NSCLC cells with common EGFR mutations. ADCC activity was positively correlated with EGFR expression in tumor cells. Studies using MET-knockout NSCLC cells revealed that MET enhanced ADCC activity with low concentrations of amivantamab. Thus, MET augments amivantamab binding to EGFR and augments ADCC activity at low amivantamab concentrations. These results indicate that binding to MET contributes to the increased efficacy of amivantamab in NSCLC with common EGFR mutations.  \n\n| Abbreviations: ADCC, antibody-dependent cellular toxicity; ECD, extracellular domain; EGF, epidermal growth factor; EGFR, epidermal growth factor receptor; FDA, Food and Drug Administration; HGF, hepatocyte growth factor; HS-AFM, high-speed atomic force microscopy; LDH, lactate dehydrogenase; MNC, blood mononuclear cell; NK, Natural Killer; NMFF, normal mode flexible fitting; NSCLC, nonsmall cell lung cancer; TGF, transforming growth factor; TKI, tyrosine kinase inhibitor.\u003Cbr>Shigeki Sato and Neval Yilmaz are co-first authors. |\n| --- |\n| This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.\u003Cbr>© 2025 The Author(s). Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association. |\n\n118 Cancer Science, 2026; 117:118–129  \n[https://doi.org/10.1111/cas.70228](https://do","cbCaihDWubNCZjfI","https://ap.wps.com/l/cbCaihDWubNCZjfI","pdf",6101689,12,"English","# Introduction\n## Mechanisms of action\n# Materials and methods\n## HS-AFM binding observations\n## Western blot and trimer formation\n## ADCC assays in NSCLC models\n# Results\n## MET-enhanced binding to EGFR\n## ADCC activity dependence on EGFR and MET\n# Conclusion","[{\"question\":\"What question does the study address about MET and amivantamab?\",\"answer\":\"The study examines whether MET contributes to amivantamab’s binding to EGFR and whether this affects amivantamab-induced ADCC.\"},{\"question\":\"How did the researchers observe amivantamab binding to EGFR and MET?\",\"answer\":\"They used high-speed atomic force microscopy (HS-AFM) to visualize real-time binding to EGFR-ECD and MET-ECD and to visualize binding involving EGFR domain 3 and the MET Sema domain.\"},{\"question\":\"What role does MET play in ADCC activity and under what amivantamab conditions?\",\"answer\":\"MET enhances mononuclear cell-mediated ADCC in NSCLC with common EGFR mutations, with stronger enhancement observed at low concentrations of amivantamab; ADCC activity also correlates with EGFR expression in tumor cells.\"}]","MET Enhances Amivantamab Binding to EGFR and Antibody-Dependent Cellular Toxicity - Cancer Science Original Article | PDF",1790733942]