{"doi":"10.1172/jci138416","title":"Antigen-specific B cell depletion for precision therapy of mucosal pemphigus vulgaris","abstract":"Desmoglein 3 chimeric autoantibody receptor T cells (DSG3-CAART) expressing the pemphigus vulgaris (PV) autoantigen DSG3 fused to CD137-CD3ζ signaling domains, represent a precision cellular immunotherapy approach for antigen-specific B cell depletion. Here, we present definitive preclinical studies enabling a first-in-human trial of DSG3-CAART for mucosal PV. DSG3-CAART specifically lysed human anti-DSG3 B cells from PV patients and demonstrated activity consistent with a threshold dose in vivo, resulting in decreased target cell burden, decreased serum and tissue-bound autoantibodies, and increased DSG3-CAART engraftment. In a PV active immune model with physiologic anti-DSG3 IgG levels, DSG3-CAART inhibited antibody responses against pathogenic DSG3 epitopes and autoantibody binding to epithelial tissues, leading to clinical and histologic resolution of blisters. DSG3 autoantibodies stimulated DSG3-CAART IFN-γ secretion and homotypic clustering, consistent with an activated phenotype. Toxicology screens using primary human cells and high-throughput membrane proteome arrays did not identify off-target cytotoxic interactions. These preclinical data guided the trial design for DSG3-CAART and may help inform CAART preclinical development for other antibody-mediated diseases.","journal":"Journal of Clinical Investigation","year":2020,"id":51421,"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":157,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9579,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":257343,"name":"Daniel K. Lundgren","orcid":null,"position":1,"is_corresponding":false},{"id":256411,"name":"Xuming Mao","orcid":"0000-0003-4232-8103","position":2,"is_corresponding":false},{"id":256412,"name":"Sílvio M. Vieira","orcid":"0000-0001-8036-4223","position":3,"is_corresponding":false},{"id":257344,"name":"Selene Nuñez-Cruz","orcid":null,"position":4,"is_corresponding":false},{"id":256413,"name":"Erik F. Williams","orcid":"0000-0002-3213-093X","position":5,"is_corresponding":false},{"id":94285,"name":"Charles-Antoine Assenmacher","orcid":"0000-0003-0073-2730","position":6,"is_corresponding":false},{"id":239925,"name":"Enrico Radaelli","orcid":"0000-0002-2885-0221","position":7,"is_corresponding":false},{"id":256414,"name":"Sangwook Oh","orcid":"0000-0003-0092-9031","position":8,"is_corresponding":false},{"id":257345,"name":"Baomei Wang","orcid":null,"position":9,"is_corresponding":false},{"id":256415,"name":"Christoph T. Ellebrecht","orcid":"0000-0001-7656-0491","position":10,"is_corresponding":false},{"id":256416,"name":"Joseph A. Fraietta","orcid":"0000-0001-7900-8993","position":11,"is_corresponding":false},{"id":242813,"name":"Michael C. Milone","orcid":"0000-0002-1580-9844","position":12,"is_corresponding":false},{"id":208025,"name":"Aimee Payne","orcid":"0000-0001-9389-7918","position":13,"is_corresponding":false},{"id":256410,"name":"Jinmin Lee","orcid":"0000-0002-0625-658X","position":0,"is_corresponding":true}],"reference_count":29,"raw_metadata":null,"created_at":"2026-07-18T20:40:28.278215Z","pmid":"32817591","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":[]}