{"doi":"10.3389/fonc.2025.1663743","title":"Anti-lipolysis-stimulated lipoprotein receptor antibody-drug conjugate to treat triple-negative breast cancer","abstract":"Triple-negative breast cancer (TNBC), the most aggressive breast cancer subtype (ER - /PR - /HER2 - ), is characterized by rapid proliferation, high metastatic rate and frequent recurrence. The development of targeted therapies for TNBC, such as antibody-drug conjugates (ADCs), has been limited by the lack of promising cell surface receptors. Our recent findings revealed that lipolysis-stimulated lipoprotein receptor (LSR) is overexpressed in breast cancer patients. The objective of this study was to develop an anti-LSR monoclonal antibody (mAb) and ADC for TNBC treatment. We observed high transcript and surface expression of LSR across various breast cancer subtypes, with over 63% of TNBC patient tissue samples exhibiting elevated expression. A new mAb targeting the extracellular domain of LSR was developed, engineered, and evaluated in vitro and in vivo . The ADC, constructed by conjugating LSR mAb with a cytotoxic agent mertansine (DM1), demonstrated potent anti-TNBC cytotoxicity in three cell lines. In vivo anti-cancer efficacy was evaluated in two TNBC xenografted mouse models, where a 24 mg/kg-body weight dose of LSR mAb-DM1 reduced tumor burden by 85% in one model and prevented tumor regrowth in the second model. Notably, no off-target effects or systemic toxicity were observed in animal models during or after treatment. This study highlights LSR as a promising therapeutic target and the anti-LSR mAb and ADC as potential targeted therapies for TNBC.","journal":"Frontiers in Oncology","year":2025,"id":546968,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.958,"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":1231026,"name":"Davis Ballard","orcid":null,"position":1,"is_corresponding":false},{"id":1239889,"name":"Tanvi Varadkar","orcid":null,"position":2,"is_corresponding":false},{"id":1208837,"name":"Jiashuai Zhang","orcid":"0000-0001-8953-8963","position":3,"is_corresponding":false},{"id":1439000,"name":"Zhenggui Du","orcid":"0000-0002-7412-0270","position":4,"is_corresponding":false},{"id":1209333,"name":"Ashley George","orcid":null,"position":5,"is_corresponding":false},{"id":1439416,"name":"Aaron Krabacher","orcid":null,"position":6,"is_corresponding":false},{"id":1439417,"name":"Rachel Yengo","orcid":null,"position":7,"is_corresponding":false},{"id":501277,"name":"Lufang Zhou","orcid":"0000-0002-1321-8442","position":8,"is_corresponding":false},{"id":418142,"name":"Margaret Liu","orcid":"0000-0002-4617-9750","position":9,"is_corresponding":false},{"id":893270,"name":"Zhuoxin “Zora” Zhou","orcid":"0009-0006-2669-9595","position":0,"is_corresponding":true}],"reference_count":67,"raw_metadata":null,"created_at":"2026-07-19T02:53:36.567932Z","pmid":"41040511","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":[]}