{"doi":"10.1371/journal.pone.0254247","title":"Attenuating nicotine’s effects with high affinity human anti-nicotine monoclonal antibodies","abstract":"Use of nicotine-specific monoclonal antibodies (mAbs) to sequester and reduce nicotine distribution to brain has been proposed as a therapeutic approach to treat nicotine addiction (the basis of tobacco use disorder). A series of monoclonal antibodies with high affinity for nicotine (nic•mAbs) was isolated from B-cells of vaccinated smokers. Genes encoding 32 unique nicotine binding antibodies were cloned, and the mAbs expressed and tested by surface plasmon resonance to determine their affinity for S-(-)-nicotine. The highest affinity nic•mAbs had binding affinity constants (KD) between 5 and 67 nM. The 4 highest affinity nic•mAbs were selected to undergo additional secondary screening for antigen-specificity, protein properties (including aggregation and stability), and functional in vivo studies to evaluate their capacity for reducing nicotine distribution to brain in rats. The 2 most potent nic•mAbs in single-dose nicotine pharmacokinetic experiments were further tested in a dose-response in vivo study. The most potent lead, ATI-1013, was selected as the lead candidate based on the results of these studies. Pretreatment with 40 and 80 mg/kg ATI-1013 reduced brain nicotine levels by 56 and 95%, respectively, in a repeated nicotine dosing experiment simulating very heavy smoking. Nicotine self-administration was also significantly reduced in rats treated with ATI-1013. A pilot rat 30-day repeat-dose toxicology study (4x200mg/kg ATI-1013) in the presence of nicotine indicated no drug-related safety concerns. These data provide evidence that ATI-1013 could be a potential therapy for the treatment of nicotine addiction.","journal":"PLoS ONE","year":2021,"id":184886,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":10,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9573,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":741452,"name":"Nicola Beltraminelli","orcid":null,"position":1,"is_corresponding":false},{"id":741453,"name":"Stephanie Fallot","orcid":null,"position":2,"is_corresponding":false},{"id":435002,"name":"Mark LeSage","orcid":null,"position":3,"is_corresponding":false},{"id":741454,"name":"Amy Saykao","orcid":null,"position":4,"is_corresponding":false},{"id":741455,"name":"Paul R. Pentel","orcid":null,"position":5,"is_corresponding":false},{"id":741456,"name":"Steve Fuller","orcid":null,"position":6,"is_corresponding":false},{"id":740811,"name":"Thomas Thisted","orcid":"0009-0006-8626-8615","position":7,"is_corresponding":false},{"id":741457,"name":"Zuzanna Biesova","orcid":null,"position":8,"is_corresponding":false},{"id":304996,"name":"Stephen Horrigan","orcid":"0000-0003-3055-7101","position":9,"is_corresponding":false},{"id":740812,"name":"Darryl Sampey","orcid":"0000-0002-5508-4075","position":10,"is_corresponding":false},{"id":516301,"name":"Bin Zhou","orcid":"0000-0001-5779-9085","position":11,"is_corresponding":false},{"id":741458,"name":"Matthew W. Kalnik","orcid":null,"position":12,"is_corresponding":false},{"id":740810,"name":"Michael D. Raleigh","orcid":"0000-0002-9715-6962","position":0,"is_corresponding":true}],"reference_count":73,"raw_metadata":null,"created_at":"2026-07-18T23:48:34.992499Z","pmid":"34329335","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":[]}