{"doi":"10.3389/fphar.2022.856961","title":"Physiological Considerations for Modeling in vivo Antibody-Target Interactions","abstract":"The number of therapeutic antibodies in development pipelines is increasing rapidly. Despite superior success rates relative to small molecules, therapeutic antibodies still face many unique development challenges. There is often a translational gap from their high target affinity and specificity to the therapeutic effects. Tissue microenvironment and physiology critically influence antibody-target interactions contributing to apparent affinity alterations and dynamic target engagement. The full potential of therapeutic antibodies will be further realized by contextualizing antibody-target interactions under physiological conditions. Here we review how local physiology such as physical stress, biological fluid, and membrane characteristics could influence antibody-target association, dissociation, and apparent affinity. These physiological factors in the early development of therapeutic antibodies are valuable toward rational antibody engineering, preclinical candidate selection, and lead optimization.","journal":"Frontiers in Pharmacology","year":2022,"id":247155,"datarank":0.5333022092234121,"base_score":3.5553480614894135,"endowment":3.5553480614894135,"self_citation_contribution":0.5333022092234121,"citation_network_contribution":0.0,"self_endowment_contribution":0.5333022092234121,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":34,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9518,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":440083,"name":"Yanguang Cao","orcid":"0000-0002-3974-9073","position":1,"is_corresponding":false},{"id":884563,"name":"Tyler Dunlap","orcid":"0000-0003-0385-9219","position":0,"is_corresponding":true}],"reference_count":124,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T00:23:53.369530Z","pmid":"35281913","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":[]}