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The study demonstrates that TAVO412, a tri-specific EGFR/cMet/VEGF antibody, can drive antitumor activity in preclinical TNBC models by inhibiting EGFR- and cMet-mediated proliferation, enhancing Fc-mediated effector functions, and suppressing angiogenesis. The dual-epitope anti-EGFR/anti-cMet design shows improved signaling inhibition and cytotoxicity in EGFR-low expressing cell lines compared with a marketed EGFR/cMet bispecific. TAVO412 also exhibits antitumor activity across multiple TNBC cell line-derived xenograft models, supporting its preclinical utility.",{"@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/a-tri-specific-egfrcmetvegf-antibody-demonstrates-potent-multi-mechanistic-activity-in-preclinical-triple-negative-breast-cancer-models-research-article/349309/",{"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/a-tri-specific-egfrcmetvegf-antibody-demonstrates-potent-multi-mechanistic-activity-in-preclinical-triple-negative-breast-cancer-models-research-article/349309.png","ImageObject",300,407,{"name":92,"@type":93},"McGucket","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-09-23","2026-09-22",true,{"@type":102,"interactionType":103,"userInteractionCount":14},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What is the main therapeutic goal of TAVO412 in TNBC?","Question",{"text":112,"@type":113},"TAVO412 is designed to simultaneously inhibit EGFR, cMet, and VEGF-driven biology in TNBC to produce a more comprehensive blockade of tumor growth and survival mechanisms.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"Which biological activities does TAVO412 demonstrate preclinically?",{"text":117,"@type":113},"TAVO412 inhibits EGFR- and cMet-mediated tumor proliferation, enhances Fc-mediated effector functions, and suppresses angiogenesis.",{"name":119,"@type":110,"acceptedAnswer":120},"How does TAVO412 compare with an existing EGFR/cMet bispecific antibody in the study?",{"text":121,"@type":113},"The study reports that the avidity of TAVO412’s dual-epitope design yields better signaling inhibition and cytotoxicity against EGFR-low expressing tumor cell lines than the JNJ-61186372 analog.","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},349309,1790207636,{"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":14,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":145},1236954412713,"https://us-avatar.wpscdn.com/davatar_29158cc5080c5b710cf443261637dec0","RESEARCH ARTICLE  \nA tri-specific EGFR/cMet/VEGF antibody demonstrates potent multi-mechanistic activity in preclinical triple-negative breast cancer models  \nReceived for publication, August 18, 2025, and in revised form, April 4, 2026 Published, Papers in Press, April 30, 2026 [https://doi.org/10.1016/j.jbc.2026.1](https://doi.org/10.1016/j.jbc.2026.1)13100  \nPu Pu1, Ying Jin1, Songling Zhang1, Yuqiang Xu1, Peng Chen1, Fulai Zhou1, Ping Sun1, Hao Jiang1, Sheng Huang1,  \nLimin Chen 1, Meixia Fu 1, ZhengXia Zha 1, Maria P. MacWilliams 1,2, and Mark L. Chiu 1,2,*  \nFrom the 1Research & Development Department, Tavotek Biotherapeutics, Suzhou, Jiang Su, China; 2Research & Development, Tavotek Biotherapeutics, Lower Gwynedd, Pennsylvania, USA  \nReviewed by members of the JBC Editorial Board. Edited by Patrick J. O’Brien  \nTriple negative breast cancer (TNBC) is a cancer with significant unmet medical needs and comprises 10 to 15% of all breast cancers and 15 to 20% of advanced breast cancers due to the limited therapeutic options. Many TNBC tumors are driven by aberrant activities of epidermal growth factor receptor (EGFR), mesenchymal epithelial transition factor (cMet), and vascular endothelial growth factor. We demonstrated how TAVO412, a tri-specific antibody that recognized cMet, dual epitopes of EGFR, and vascular endothelial growth factor could elicit antitumor activity in TNBC. TAVO412 showed inhibition of EGFR- and cMet-mediated tumor proliferation, enhanced Fc-mediated effector functions, and suppression of angiogenesis. The avidity of the dual-epitope based anti-EGFR and anti-cMet design had better signaling inhibition and cytotoxicity against EGFR-low expressing tumor cell lines than the JNJ-61186372 analog, a marketed EGFR/cMet bispecific antibody. Furthermore, TAVO412 exhibited antitumor activities in multiple TNBC cell line-derived xenograft models. Overall, TAVO412 demonstrated great preclinical utility against TNBC.  \nTriple negative breast cancers (TNBCs) are aggressive subtypes of breast cancers lacking the estrogen and progesterone receptors and display low-levels of human epidermal growth factor receptor 2 (1–3). TNBCs account for 10 to 15% of all breast cancers and 15 to 20% of advanced breast cancers, and is associated with rapid progression, early relapse, and limited therapeutic options. Current first-line therapies rely mainly on combination chemotherapy or immune checkpoint blockade, yet TNBC often progresses more rapidly than other subtypes, leading to poor outcomes and limited long-term control (1, 4, 5).  \nA major challenge in TNBC is the high degree of molecular heterogeneity and the rapid emergence of drug-resistant subclones. Single-target therapies—including tyrosine kinase inhibitors (TKIs) and monospecific antibodies-often produce only transient responses before resistance develops through  \n* For correspondence: Mark L. Chiu, [Mark.Chiu@tavotek.com](Mark.Chiu@tavotek.com).  \ntarget loss, mutation, or compensatory pathway activation. In contrast, multi-targeting agents can suppress parallel oncogenic pathways and reduce the likelihood of simultaneous resistance-conferring mutations, offering a more durable therapeutic approach (6).  \nMany TNBC patients have tumors with increased levels of EGFR, and cMet (7–10). Concomitantly, the activation of the EGFR signaling pathway enhances vascular endothelial growth factor type A (VEGF-A) secretion that then promotes angiogenesis and tumor growth, resistance to EGFR directed therapies such as cetuximab (anti (α)-EGFR mAb), and gefitinib (EGFR TKI), and shorter survival in TNBC patients (11–15). Similarly, cMet overexpression and hepatocyte growth factor (HGF)–mediated activation contribute to resistance to EGFR TKIs and are associated with inferior clinical outcomes (16–19). High-level co-expression of EGFR and cMet in TNBC is associated with significantly worse disease-free survival than expression of EGFR alone. Combined inhibition of EGFR and cMet sign","cbCaivGvrcIFb2oc","https://ap.wps.com/l/cbCaivGvrcIFb2oc","pdf",6958172,13,"English","# Background and unmet needs in TNBC\n## Target biology: EGFR, cMet, and VEGF signaling crosstalk\n## Limitations of single-target therapies and anti-VEGF toxicity\n# Rationale for tri-specific targeting\n## Multi-targeting to reduce resistance likelihood\n# TAVO412 design and intended mechanisms\n## cMet binding, dual EGFR epitopes, and VEGF targeting\n# Preclinical evidence of activity","[{\"question\":\"What is the main therapeutic goal of TAVO412 in TNBC?\",\"answer\":\"TAVO412 is designed to simultaneously inhibit EGFR, cMet, and VEGF-driven biology in TNBC to produce a more comprehensive blockade of tumor growth and survival mechanisms.\"},{\"question\":\"Which biological activities does TAVO412 demonstrate preclinically?\",\"answer\":\"TAVO412 inhibits EGFR- and cMet-mediated tumor proliferation, enhances Fc-mediated effector functions, and suppresses angiogenesis.\"},{\"question\":\"How does TAVO412 compare with an existing EGFR/cMet bispecific antibody in the study?\",\"answer\":\"The study reports that the avidity of TAVO412’s dual-epitope design yields better signaling inhibition and cytotoxicity against EGFR-low expressing tumor cell lines than the JNJ-61186372 analog.\"}]","A tri-specific EGFR/cMet/VEGF antibody demonstrates potent multi-mechanistic activity in preclinical triple-negative breast cancer models - research article | PDF",1790082690,33]