{"doi":"10.1016/j.ymthe.2025.02.029","title":"ZP4: A novel target for CAR-T cell therapy in triple negative breast cancer","abstract":"Triple-negative breast cancer (TNBC) remains one of the most challenging subtypes of breast cancer to treat due to a lack of effective targeted therapies. Chimeric antigen receptor (CAR)-T cells hold promise, but their efficacy in solid tumors is often limited by on-target/off-tumor toxicities. Through comprehensive bioinformatic analysis of public RNA and proteomic data, we identified zona pellucida glycoprotein 4 (ZP4) as a novel target for TNBC. ZP4 RNA and protein were detected in a subset of TNBC patient samples and patient-derived xenograft (PDX) models, with expression otherwise restricted to oocytes. We generated 89 ZP4-specific novel monoclonal antibodies and used the single-chain variable fragment (scFv) antigen binding domains from the top three candidates to engineer CAR constructs. ZP4 CAR-T cells demonstrated efficacy against ZP4-expressing TNBC cells and PDX models. Additionally, we found that variations in the scFv antigen binding domain significantly influence CAR-T cell function.","journal":"Molecular Therapy","year":2025,"id":538835,"datarank":0.20794415416798362,"base_score":1.3862943611198906,"endowment":1.3862943611198906,"self_citation_contribution":0.20794415416798362,"citation_network_contribution":0.0,"self_endowment_contribution":0.20794415416798362,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":3,"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":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":51820,"name":"Jonathan T. Lei","orcid":"0000-0002-0209-8051","position":1,"is_corresponding":false},{"id":411772,"name":"Xinpei Yi","orcid":"0000-0001-8562-1655","position":2,"is_corresponding":false},{"id":1078087,"name":"Diego F. Chamorro","orcid":"0000-0003-1236-8120","position":3,"is_corresponding":false},{"id":312920,"name":"Paul Shafer","orcid":null,"position":4,"is_corresponding":false},{"id":240486,"name":"Ahmed Z. Gad","orcid":"0000-0002-6149-3414","position":5,"is_corresponding":false},{"id":379377,"name":"Lacey E. Dobrolecki","orcid":"0000-0001-6839-629X","position":6,"is_corresponding":false},{"id":1426094,"name":"Emily Madaras","orcid":null,"position":7,"is_corresponding":false},{"id":240513,"name":"Nabil Ahmed","orcid":"0000-0002-0982-8424","position":8,"is_corresponding":false},{"id":30176,"name":"Michael T. Lewis","orcid":"0000-0002-6330-4007","position":9,"is_corresponding":false},{"id":1204209,"name":"Bing Zhang","orcid":"0000-0002-3953-0290","position":10,"is_corresponding":false},{"id":646562,"name":"Valentina Hoyos","orcid":"0000-0002-8269-6341","position":11,"is_corresponding":false},{"id":1078088,"name":"Lauren K. Somes","orcid":"0000-0002-1788-9622","position":0,"is_corresponding":true}],"reference_count":92,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:52:25.799399Z","pmid":"39980195","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":[]}