000163138 001__ 163138
000163138 005__ 20251009145936.0
000163138 0247_ $$2doi$$a10.1038/s41589-025-01971-8
000163138 0248_ $$2sideral$$a145634
000163138 037__ $$aART-2025-145634
000163138 041__ $$aeng
000163138 100__ $$0(orcid)0000-0002-3122-9401$$aHurtado-Guerrero, Ramón
000163138 245__ $$aStructure-guided phage display discovery of antibodies for (S)Tn-glycans in protein context
000163138 260__ $$c2025
000163138 5203_ $$aDeveloping high-affinity monoclonal antibodies (mAbs) against tumor-associated carbohydrate antigens such as Tn and STn on carrier proteins remains a major challenge in cancer therapy. These antigens, expressed as glycan–peptide epitopes (combotopes), require precise recognition for high specificity. Through structural studies, we found that VH domains of certain antibodies primarily recognize glycans, whereas VL domains bind peptide sequences. Using these insights, we developed a VH-focused and VL-diverse phage display library to discover mAbs with combotope-binding characteristics. Notably, structural analysis enabled us to convert Tn-specific mAbs into STn-specific mAbs through modification of VH complementarity-determining region 3, demonstrating the versatility of this approach. Our hypothesis was validated with glycoprotein targets MUC1 and CD43, yielding antibodies with high specificity and affinity. Furthermore, internalization studies using the parental antibody scaffold show efficient uptake by tumor cells, supporting its use in antibody–drug conjugates. This platform addresses the challenge of generating glycoform-specific antibodies for cancer therapy.
000163138 536__ $$9info:eu-repo/grantAgreement/ES/AEI/PID2019-105451GB-I00$$9info:eu-repo/grantAgreement/ES/DGA/E34-23R$$9info:eu-repo/grantAgreement/ES/DGA-FEDER/E34-R17$$9info:eu-repo/grantAgreement/ES/DGA/LMP58-18$$9info:eu-repo/grantAgreement/EC/FP7/316929/EU/Joined efforts to fight gastric cancer/GastricGlycoExplorer$$9info:eu-repo/grantAgreement/EC/H2020/814029/EU/Synthetic biology of carbohydrate-binding proteins: engineering protein-carbohydrate interactions for diagnostics and cell targeting$$9This project has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No H2020 814029-synBIOcarb$$9info:eu-repo/grantAgreement/ES/MICINN AEI/PID2022-136362NB-I00$$9info:eu-repo/grantAgreement/ES/MICINN/PID2021-127622OB-I00$$9info:eu-repo/grantAgreement/ES/MICINN/PID2022-137973NB-I00
000163138 540__ $$9info:eu-repo/semantics/closedAccess$$aAll rights reserved$$uhttp://www.europeana.eu/rights/rr-f/
000163138 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000163138 700__ $$aSpyridon, Gatos
000163138 700__ $$aGinés-Alcober, Irene
000163138 700__ $$0(orcid)0000-0001-6815-6720$$aMacías-León, Javier
000163138 700__ $$0(orcid)0000-0002-5838-0857$$aGonzález-Ramírez, Andrés Manuel
000163138 700__ $$aKasapoglu, Ilknur
000163138 700__ $$aVeloz, Billy$$uUniversidad de Zaragoza
000163138 700__ $$aCompañón, Ismael
000163138 700__ $$aGhirardello, Mattia
000163138 700__ $$0(orcid)0000-0002-2202-3460$$aMerino, Pedro$$uUniversidad de Zaragoza
000163138 700__ $$aCorzana, Francisco
000163138 700__ $$aBlixt, Ola
000163138 7102_ $$12013$$2765$$aUniversidad de Zaragoza$$bDpto. Química Orgánica$$cÁrea Química Orgánica
000163138 7102_ $$11002$$2060$$aUniversidad de Zaragoza$$bDpto. Bioq.Biolog.Mol. Celular$$cÁrea Bioquímica y Biolog.Mole.
000163138 773__ $$g(2025), [18 pp.]$$pNat. Chem. Biol.$$tNature Chemical Biology$$x1552-4450
000163138 8564_ $$s4893605$$uhttps://zaguan.unizar.es/record/163138/files/texto_completo.pdf$$yVersión publicada
000163138 8564_ $$s2522693$$uhttps://zaguan.unizar.es/record/163138/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000163138 909CO $$ooai:zaguan.unizar.es:163138$$particulos$$pdriver
000163138 951__ $$a2025-10-08-12:59:57
000163138 980__ $$aARTICLE