{"doi":"10.1016/j.omto.2023.09.002","title":"Preclinical assessment of a novel human antibody VH domain targeting mesothelin as an antibody-drug conjugate","abstract":null,"journal":"Molecular Therapy - Oncolytics","year":2023,"id":650450,"datarank":0.41588830833596724,"base_score":2.772588722239781,"endowment":2.772588722239781,"self_citation_contribution":0.41588830833596724,"citation_network_contribution":0.0,"self_endowment_contribution":0.41588830833596724,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":15,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1261917,"name":"Xiaojie Chu","orcid":"0000-0003-3345-9283","position":1,"is_corresponding":false},{"id":765528,"name":"Cynthia Adams","orcid":"0000-0001-7688-8518","position":2,"is_corresponding":false},{"id":546095,"name":"Tatiana V. Ilina","orcid":"0000-0002-9985-5978","position":3,"is_corresponding":false},{"id":546606,"name":"Michel Guerrero","orcid":null,"position":4,"is_corresponding":false},{"id":1177576,"name":"Guowu Lin","orcid":"0000-0002-0823-0105","position":5,"is_corresponding":false},{"id":1212221,"name":"Chuan Chen","orcid":"0009-0004-3157-8849","position":6,"is_corresponding":false},{"id":1696021,"name":"Dontcho Jelev","orcid":null,"position":7,"is_corresponding":false},{"id":546097,"name":"Rieko Ishima","orcid":"0000-0002-3418-0922","position":8,"is_corresponding":false},{"id":717111,"name":"Wei Li","orcid":"0000-0002-7530-4872","position":9,"is_corresponding":false},{"id":258969,"name":"John W. Mellors","orcid":"0000-0002-3737-9742","position":10,"is_corresponding":false},{"id":671375,"name":"Guillermo Calero","orcid":"0000-0003-3730-4676","position":11,"is_corresponding":false},{"id":267233,"name":"Dimiter S. Dimitrov","orcid":"0000-0002-2258-1024","position":12,"is_corresponding":false},{"id":267224,"name":"Zehua Sun","orcid":"0000-0003-4287-1763","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Preclinical assessment of a novel human antibody VH domain targeting mesothelin as an antibody-drug conjugate","abstract":"Mesothelin (MSLN) has been a validated tumor-associated antigen target for several solid tumors for over a decade, making it an attractive option for therapeutic interventions. Novel antibodies with high affinity and better therapeutic properties are needed. In the current study, we have isolated and characterized a novel heavy chain variable (VH) domain 3C9 from a large-size human immunoglobulin VH domain library. 3C9 exhibited high affinity (KD [dissociation constant] <3 nM) and binding specificity in a membrane proteome array (MPA). In a mouse xenograft model, 3C9 fused to human IgG1 Fc was detected at tumor sites as early as 8 h post-infusion and remained at the site for over 10 days. Furthermore, 3C9 fused to a human Fc domain drug conjugate effectively inhibited MSLN-positive tumor growth in a mouse xenograft model. The X-ray crystal structure of full-length MSLN in complex with 3C9 reveals interaction of the 3C9 domains with two distinctive residue patches on the MSLN surface. This newly discovered VH antibody domain has a high potential as a therapeutic candidate for MSLN-expressing cancers.","is_dataset_classified":null,"base_score":2.772588722239781,"endowment":2.772588722239781,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"37771390","pmcid":null,"openalex_id":"https://openalex.org/W4386630251","authors":[],"funders":[],"total_grants":0,"fwci":2.8309,"citation_percentile":0.91752005,"influential_citations":0,"citation_trend":[{"year":2023,"count":1},{"year":2024,"count":3},{"year":2025,"count":10},{"year":2026,"count":1}],"oa_status":"gold","license":"cc-by-nc-nd","oa_locations":[{"url":"http://www.cell.com/article/S2372770523000694/pdf","host_type":"journal"},{"url":"http://www.cell.com/article/S2372770523000694/pdf","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S2372770523000694?httpAccept=text/xml","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S2372770523000694?httpAccept=text/plain","host_type":"publisher"},{"url":"https://doi.org/10.1016/j.omto.2023.09.002","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/37771390","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/10522976","host_type":"repository"},{"url":"https://doaj.org/article/e3ac5eca01cc47a6b9a22161f0b5c4b7","host_type":"repository"},{"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC10522976/pdf/main.pdf","host_type":"repository"}],"fields_of_study":["Eosinophilic Disorders and Syndromes","Galectins and Cancer Biology","Monoclonal and Polyclonal Antibodies Research"],"mesh_terms":[],"keywords":["Mesothelin","Conjugate","Antibody-drug conjugate","Antibody","Drug","Medicine","Cancer research","Pharmacology","Immunology","Monoclonal antibody","Mathematics"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-10T05:30:57.266459Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}