{"doi":"10.1172/jci.insight.172914","title":"A CD6-targeted antibody-drug conjugate as a potential therapy for T cell–mediated disorders","abstract":"The selective targeting of pathogenic T cells is a holy grail in the development of new therapeutics for T cell-mediated disorders, including many autoimmune diseases and graft versus host disease. We describe the development of a CD6-targeted antibody-drug conjugate (CD6-ADC) by conjugating an inactive form of monomethyl auristatin E (MMAE), a potent mitotic toxin, onto a mAb against CD6, an established T cell surface marker. Even though CD6 is present on all T cells, only the activated (pathogenic) T cells vigorously divide and thus are susceptible to the antimitotic MMAE-mediated killing via the CD6-ADC. We found CD6-ADC selectively killed activated proliferating human T cells and antigen-specific mouse T cells in vitro. Furthermore, in vivo, whereas the CD6-ADC had no significant detrimental effect on normal T cells in naive CD6-humanized mice, the same dose of CD6-ADC, but not the controls, efficiently treated 2 preclinical models of autoimmune uveitis and a model of graft versus host disease. These results provide evidence suggesting that CD6-ADC could be further developed as a potential therapeutic agent for the selective elimination of pathogenic T cells and treatment of many T cell-mediated disorders.","journal":"JCI Insight","year":2023,"id":343527,"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":14,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9541,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1080629,"name":"Liping Luo","orcid":"0000-0002-2673-9749","position":1,"is_corresponding":false},{"id":399095,"name":"Jin Chen","orcid":"0000-0002-9622-5962","position":2,"is_corresponding":false},{"id":477807,"name":"Rupesh Singh","orcid":"0000-0002-0938-9388","position":3,"is_corresponding":false},{"id":278887,"name":"William M. Baldwin","orcid":"0000-0002-7271-1827","position":4,"is_corresponding":false},{"id":247327,"name":"David A. Fox","orcid":"0000-0002-0230-6607","position":5,"is_corresponding":false},{"id":323647,"name":"Daniel J. Lindner","orcid":"0000-0002-8296-7703","position":6,"is_corresponding":false},{"id":258446,"name":"Daniel Martín","orcid":"0000-0003-4488-2538","position":7,"is_corresponding":false},{"id":251060,"name":"Rachel R Caspi","orcid":"0000-0002-7140-7671","position":8,"is_corresponding":false},{"id":977604,"name":"Lin Feng","orcid":"0000-0002-6208-4436","position":9,"is_corresponding":false},{"id":380321,"name":"Lingjun Zhang","orcid":"0000-0001-7549-3813","position":0,"is_corresponding":true}],"reference_count":26,"raw_metadata":null,"created_at":"2026-07-19T01:11:21.758449Z","pmid":"37917882","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":[]}