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Many TIL subsets express the co-stimulatory receptor CD27, enabling potential T-cell re-activation, but CD27 agonist antibodies have limited clinical responses because they require higher-order receptor cross-linking. This study reports CD27xEGFR, a bispecific Fc-silent antibody that targets CD27 and EGFR to drive EGFR-restricted CD27 co-stimulation and potent T-cell responses, including proliferation, activation markers, cytokine release, and effector-to-target–dependent tumor cell killing.",{"@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":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/egfr-selective-activation-of-cd27-co-stimulatory-signaling-by-a-bispecific-antibody-enhances-anti-tumor-activity-of-t-cells/383902/",{"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/egfr-selective-activation-of-cd27-co-stimulatory-signaling-by-a-bispecific-antibody-enhances-anti-tumor-activity-of-t-cells/383902.png","ImageObject",300,407,{"name":92,"@type":93},"Taylor Morgan","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-29","2026-09-24",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},"What problem does CD27xEGFR aim to solve in T-cell anti-tumor immunity?","Question",{"text":112,"@type":113},"It addresses limited responses from current immune checkpoint inhibitors by providing additional co-stimulatory activation through CD27, overcoming suppression within the tumor microenvironment.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How is CD27xEGFR designed to activate CD27 signaling?",{"text":117,"@type":113},"CD27xEGFR is a bispecific, Fc-silent antibody that binds both CD27 and EGFR, enabling EGFR-restricted localization that promotes cancer cell-localized CD27 cross-linking and activation.",{"name":119,"@type":110,"acceptedAnswer":120},"What immune and functional readouts were used to evaluate CD27xEGFR activity?",{"text":121,"@type":113},"The study assesses T-cell proliferation, activation markers, cytotoxicity, IFN-γ release, and effector-to-target ratio–dependent elimination of cancer cells in model systems.","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},383902,1790293841,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"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":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":36},1099523885336,"https://ap-avatar.wpscdn.com/davatar_276721f389ce27ea32af1340a28f341c","TYPE Original Research PUBLISHED 20 July 2023  \nDOI 10.3389/fimmu.2023.1191866  \nOPEN ACCESS  \nEDITED BY  \nAdam Zwolak,  \nJanssen Research and Development, United States  \nREVIEWED BY  \nInger Øynebråten,  \nOslo University Hospital, Norway Shahram Salek-Ardakani, Pfizer, United States  \n*CORRESPONDENCE Edwin Bremer  \n [e.bremer@umcg.nl](e.bremer@umcg.nl)  \nRECEIVED 22 March 2023  \nACCEPTED 03 July 2023  \nPUBLISHED 20 July 2023  \nCITATION  \nMelo V, Nelemans LC, Vlaming M, Lourens HJ, Wiersma VR, Bilemjian V, Huls G, de Bruyn M and Bremer E (2023)  \nEGFR-selective activation of CD27 co-stimulatory signaling by a bispecific antibody enhances anti-tumor activity of T cells.  \nFront. Immunol. 14:1191866 .  \ndoi: 10.3389/fimmu.2023.1191866  \nCOPYRIGHT  \n© 2023 Melo, Nelemans, Vlaming, Lourens, Wiersma, Bilemjian, Huls, de Bruyn and Bremer. 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.  \nEGFR-selective activation of CD27 co-stimulatory signaling by a bispecific antibody enhances anti-tumor activity of T cells  \nVinicio Melo 1, Levi Collin Nelemans 1, Martijn Vlaming 1, Harm Jan Lourens 1, Valerie R. Wiersma 1, Vrouyr Bilemjian 1, Gerwin Huls 1, Marco de Bruyn 2 and Edwin Bremer 1*  \n1 Department of Hematology, University Medical Center Groningen, University of Groningen, Groningen, Netherlands, 2 Department of Obstetrics & Gynecology, University Medical Center Groningen, University of Groningen, Groningen, Netherlands  \nA higher density of tumor infilt rating lymphocytes (TILs) in the tumor microenvironment, particularly cytotoxic CD8+ T cells, is associated with improved clinical outcome in various cancers. However, local inhibitory factors can suppress T cell activity and hinder anti-tumor immunity. Notably, TILs from various cancer types express the co-stimulatory Tumor Necrosis Factor receptor CD27, making it a potential target for co-stimulation and re-activation of tumorinfiltrated and tumor-reactive T cells. Anti-cancer therapeutics based on exploiting CD27-mediated T cell co-stimulation have proven safe, but clinical responses remain limited. This is likely because current monoclonal antibodies fail to effectively activate CD27 signaling, as this receptor requires higher-order receptor cross-linking. Here, we report on a bispecific antibody, CD27xEGFR, that targets both CD27 and the tumor antigen, epidermal growth factor receptor (EGFR) . By targeting EGFR, which is commonly expressed on carcinomas, CD27xEGFR induced cancer cell-localized crosslinking and activation of CD27 . The design of CD27xEGFR includes an Fc-silent domain, which is designed to minimize potential toxicity by reducing Fc gamma receptor-mediated binding and activation of immune cells. CD27xEGFR bound to both of its targets simultaneously and triggered EGFR-restricted co-stimulation of T cells as measured by T cell proliferation, T cell activation markers, cytotoxicity and IFN-g release. Further, CD27xEGFR augmented T cell cytotoxicity in a panel of artificial antigen-presenting carcinoma cell line models, leading to Effector-toTarget ratio-dependent elimination of cancer cells. Taken together, we present the in vitro characterization of a novel bispecific antibody that re-activates T cell immunity in EGFR-expressing cancers through targeted co-stimulation of CD27 .  \nKEYWORDS  \nimmunotherapy, bispecific antibody, CD27, EGFR, T cell, co-stimulation  \nFrontiers in Immunology 01 [frontiersin.org](frontiersin.org)  \n1 Introduction  \nThe re-activation of tumor-reactive T cells with so-called immune checkpoint inhibitors (ICIs) has translated into remarkable clinical breakthr","cbCaid0EpYKhkn1a","https://ap.wps.com/l/cbCaid0EpYKhkn1a","pdf",5918855,16,"English","# 1 Introduction\n## Tumor-reactive T cells and immune checkpoint inhibitors\n## Need for additional co-stimulatory signals in the tumor microenvironment\n## CD27 as a co-stimulatory receptor target\n## Rationale for CD27 activation","[{\"question\":\"What problem does CD27xEGFR aim to solve in T-cell anti-tumor immunity?\",\"answer\":\"It addresses limited responses from current immune checkpoint inhibitors by providing additional co-stimulatory activation through CD27, overcoming suppression within the tumor microenvironment.\"},{\"question\":\"How is CD27xEGFR designed to activate CD27 signaling?\",\"answer\":\"CD27xEGFR is a bispecific, Fc-silent antibody that binds both CD27 and EGFR, enabling EGFR-restricted localization that promotes cancer cell-localized CD27 cross-linking and activation.\"},{\"question\":\"What immune and functional readouts were used to evaluate CD27xEGFR activity?\",\"answer\":\"The study assesses T-cell proliferation, activation markers, cytotoxicity, IFN-γ release, and effector-to-target ratio–dependent elimination of cancer cells in model systems.\"}]","EGFR-selective activation of CD27 co-stimulatory signaling by a bispecific antibody enhances anti-tumor activity of T cells | PDF",1790260160]