[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"doc-seo-375912-105":3,"detail-sidebar-cat-0-en-105":81,"doc-detail-375912-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","optimization-of-adcitmer-a-monomethyl-auristatin-e-bearing-antibody-drug-conjugate-for-the-treatment-of-cd56-expressing-cancers","Optimization of Adcitmer, a Monomethyl-Auristatin E bearing antibody-drug conjugate for the treatment of CD56-expressing cancers","","The cell adhesion protein CD56 is identified as a therapeutic target across multiple solid tumors and hematological malignancies. Adcitmer, a CD56-directed antibody-drug conjugate, showed antitumor activity in preclinical Merkel cell carcinoma models. This study further optimizes Adcitmer to reduce hematologic toxicity by preventing FcγR-mediated interactions through aglycosylation. Human leukocyte and MCC cell line assays assessed effects on viability and proliferation, followed by evaluation in an MCC xenograft mouse model. Aglycosylation reduced immune cell toxicity while improving therapeutic performance, supporting its use in advanced MCC or other CD56-positive tumors.",{"@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/optimization-of-adcitmer-a-monomethyl-auristatin-e-bearing-antibody-drug-conjugate-for-the-treatment-of-cd56-expressing-cancers/375912/",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/optimization-of-adcitmer-a-monomethyl-auristatin-e-bearing-antibody-drug-conjugate-for-the-treatment-of-cd56-expressing-cancers/375912.png","ImageObject",300,407,{"name":42,"@type":43},"Alex Sinclair","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-11-04","2026-09-24",true,{"@type":52,"interactionType":53,"userInteractionCount":55},"InteractionCounter",{"@type":54},"ViewAction",8,{"@type":57,"mainEntity":58},"FAQPage",[59,65,69],{"name":60,"@type":61,"acceptedAnswer":62},"What limitation of previously tested CD56-targeting ADCs does this study address?","Question",{"text":63,"@type":64},"The study targets therapeutic limitations related to hematologic toxicity observed with earlier CD56-targeting antibody-drug conjugates, including toxic effects on leukocytes.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"How does the study reduce Adcitmer interaction with immune cells?",{"text":68,"@type":64},"It generates anaglycosylated Adcitmer to avoid FcγR binding, since glycosylation is essential for FcγR recognition.",{"name":70,"@type":61,"acceptedAnswer":71},"What were the key findings from in vitro and in vivo evaluations?",{"text":72,"@type":64},"Aglycosylated Adcitmer showed reduced immune cell toxicity and improved therapeutic performance in an MCC xenograft mouse model, even using immunodeficient mice.","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},375912,1790362985,{"code":4,"msg":82,"data":83},"success",[84,88,92,96,101,106,110,114,119,122,126],{"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":97,"doc_module":4,"doc_module_name":25,"category_name":98,"show_sort_weight":99,"slug":100},5,"Comic",60,"comic",{"id":102,"doc_module":4,"doc_module_name":25,"category_name":103,"show_sort_weight":104,"slug":105},6,"Technology",50,"technology",{"id":107,"doc_module":4,"doc_module_name":25,"category_name":29,"show_sort_weight":108,"slug":109},7,40,"healthcare",{"id":55,"doc_module":4,"doc_module_name":25,"category_name":111,"show_sort_weight":112,"slug":113},"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":97,"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":107,"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":55,"language":139,"language_code":8,"site_id":7,"html_lang":8,"table_of_contents":140,"faqs":141,"seo_title":142,"seo_description":12,"update_tm":143,"read_time":117},1099523882182,"https://ap-avatar.wpscdn.com/davatar_6f874abed73319feea01a86fa6f0fab8","Open access Short report  \nOptimization of Adcitmer, a Monomethyl-Auristatin E bearing antibody-drug conjugate for the treatment of CD56-expressing cancers  \nAurelie Drouin  ,1 Laurine Durand,1 Clara Esnault  ,1 Pauline Gaboriaud,1 Valérie Leblond,1 Shawk Karim,2 Morgane Fouché,2 Christine Dhommée,2 Christine B Baltus,3 Fanny Boursin,4 Nicolas Aubrey,4 Roland Houben,5 David Schrama,5 Serge Guyétant,1,6 Audrey Desgranges,3  \nMarie Claude Viaud-Massuard,3,7 Valérie Gouilleux-Gruart,2,8 Mahtab Samimi,1,6 Thibault Kervarrec,1,6 Antoine Touzé1  \nTo cite: Drouin A, Durand L, Esnault C, et al. Optimization of Adcitmer, a MonomethylAuristatin E bearing antibodydrug conjugate for the treatment of CD56-expressing cancers. Journal for ImmunoTherapy of Cancer 2025;13:e010897 . doi:10.1136/jitc-2024-010897  \n► Additional supplemental material is published online only. To view, please visit the journal online ([https://doi.org/10.1136/](https://doi.org/10.1136/)[ ](https://doi.org/10.1136/)[jitc-2024-010897](jitc-2024-010897)) .  \nAccepted 03 February 2025  \n© Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group.  \nFor numbered affiliations see end of article.  \nCorrespondence to  \nDr Aurelie Drouin;  \n[drouin.aurelie37@gmail.com](drouin.aurelie37@gmail.com)  \nABSTRACT  \nThe cell adhesion protein CD56 has been identified as a potential therapeutic target in several solid tumors and hematological malignancies. Recently, we developed a CD56-directed antibody-drug conjugate (ADC), called Adcitmer and demonstrated its antitumor properties in preclinical models of the rare and aggressive skin cancer Merkel cell carcinoma (MCC) .  \nThe present study aims to further optimize Adcitmer to overcome the therapeutic limitations observed with previously evaluated CD56-targeting ADCs, which were partially related to toxic effects on leukocytes. To this end, we aimed to avoid interaction of Adcitmer with immune cells via Fc gamma receptor (FcγR) binding.  \nSince glycosylation is essential for FcγR binding, anaglycosylated form of Adcitmer was generated and evaluated on human leukocytes and MCC cell lines using cell death (annexin V/ 7-aminoactinomycine D) and proliferation (2,3-Bis-(2-methoxy-4Nitro-5-sulfophenyl) - 2H-tetrazolium-5carboxanilide) assays. Finally, the therapeutic performance of Adcitmer and its aglycosylated form was assessed in an MCC xenograft mouse model. Investigating the Adcitmer interaction with immune cells demonstrated that it is mostly mediated by Fc recognition. Accordingly, Adcitmer aglycosylation led to reduced immune cell toxicity and strikingly also to improved therapeutic performance even in an MCC xenograft model using immunodeficient mice.  \nOur study suggests that aglycosylated Adcitmer should be considered as a therapeutic option in patients with advanced MCC or other CD56-positive tumors.  \nINTRODUCTION  \nAntibody-drug conjugates (ADCs) development constitutes a therapeutic field in expansion, with more than hundreds of ADCs in preclinical and clinical development and 11 molecules already approved by the Food and Drug Administration in the field of oncology.1  \nADCs consist of a monoclonal antibody anda highly potent cytotoxic agent (ie, payload), associated by a linker.2 3 The performances of these drugs rely on antibody properties,4–6 on the nature of the cytotoxic drug, but also on the bioconjugation technology.1 7 Another determinant of ADC efficiency is the bystander effect, that is, the ability of the ADC to induce cell death through the release of the cytotoxic molecule into the tumor microenvironment.8–11  \nBesides the targets of the current approved ADC, several other membrane antigens have been identified over the last few years as potentially relevant for ADC-based strategy. Among them, CD56, also known as neural cell adhesion molecule, is expressed in various neuroendocrine neoplasms including small cell lung cancer (","cbCaimqLuh2K4HAz","https://ap.wps.com/l/cbCaimqLuh2K4HAz","pdf",2291084,"English","# ABSTRACT\n# INTRODUCTION\n# MATERIALS AND METHODS\n## Cell lines\n## ADCs binding to Fc gamma receptor\n## Evaluation of toxicity","[{\"question\":\"What limitation of previously tested CD56-targeting ADCs does this study address?\",\"answer\":\"The study targets therapeutic limitations related to hematologic toxicity observed with earlier CD56-targeting antibody-drug conjugates, including toxic effects on leukocytes.\"},{\"question\":\"How does the study reduce Adcitmer interaction with immune cells?\",\"answer\":\"It generates anaglycosylated Adcitmer to avoid FcγR binding, since glycosylation is essential for FcγR recognition.\"},{\"question\":\"What were the key findings from in vitro and in vivo evaluations?\",\"answer\":\"Aglycosylated Adcitmer showed reduced immune cell toxicity and improved therapeutic performance in an MCC xenograft mouse model, even using immunodeficient mice.\"}]","Optimization of Adcitmer, a Monomethyl-Auristatin E bearing antibody-drug conjugate for the treatment of CD56-expressing cancers | PDF",1790216604]