{"doi":"10.3390/antib13040085","title":"Preventative Cancer Vaccine-Elicited Human Anti-MUC1 Antibodies Have Multiple Effector Functions","abstract":"BACKGROUND/OBJECTIVES: Mucin-1 (MUC1) is a transmembrane glycoprotein that is overexpressed and hypoglycosylated in premalignant and malignant epithelial cells compared to normal cells, creating a target antigen for humoral and cellular immunity. Healthy individuals with a history of advanced colonic adenomas and at high risk for colon cancer were enrolled in a clinical trial to evaluate the feasibility of using a MUC1 peptide vaccine to prevent colon cancer. Anti-MUC1 antibodies elicited by this vaccine were cloned using peripheral blood B cells and sera collected two weeks after a one-year booster. Twelve of these fully human monoclonal antibodies (mAb) were tested for binding to MUC1+ target cells, and three with the highest binding were further evaluated for various effector functions important for tumor rejection. METHODS: Immune cells were incubated together with target cells expressing variations in the number, distance, and membrane anchoring properties of the MUC1 epitope in the presence of each mAb. RESULTS: All three mAbs mediated antibody-dependent cytokine release (ADCR), antibody-dependent cellular cytotoxicity (ADCC), and antibody-dependent cellular phagocytosis (ADCP). Two also mediated antibody-dependent trogocytosis/trogoptosis (ADCT). None were capable of complement-dependent cytotoxicity (CDC). CONCLUSIONS: ADCP and ADCT functions were more efficient when antibodies bound epitopes proximal to and anchored to the membrane, providing insight for future therapeutic antibody validation strategies.","journal":"Antibodies","year":2024,"id":449368,"datarank":0.26876392038420827,"base_score":1.791759469228055,"endowment":1.791759469228055,"self_citation_contribution":0.26876392038420827,"citation_network_contribution":0.0,"self_endowment_contribution":0.26876392038420827,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":5,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9599,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":559131,"name":"Jason Lohmueller","orcid":"0000-0001-6089-9992","position":1,"is_corresponding":false},{"id":798652,"name":"Matthew T. Dracz","orcid":null,"position":2,"is_corresponding":false},{"id":1269132,"name":"Najla Saadallah","orcid":null,"position":3,"is_corresponding":false},{"id":1269133,"name":"Eric D. Ricci","orcid":null,"position":4,"is_corresponding":false},{"id":272162,"name":"Donella Beckwith","orcid":"0000-0002-2124-4931","position":5,"is_corresponding":false},{"id":927622,"name":"Ramya Ayyalasomayajula","orcid":"0000-0002-7610-0097","position":6,"is_corresponding":false},{"id":272163,"name":"Mare Čudić","orcid":"0000-0002-7657-0400","position":7,"is_corresponding":false},{"id":402848,"name":"Olivera J. Finn","orcid":"0000-0003-0930-920X","position":8,"is_corresponding":false},{"id":1020469,"name":"Michelle L. McKeague","orcid":null,"position":0,"is_corresponding":true}],"reference_count":88,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:02:16.291892Z","pmid":"39449327","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":[]}