{"doi":"10.18632/oncotarget.28752","title":"A novel anti-human CD25 mAb with preferential reactivity to activated T regulatory cells depletes them from the tumor microenvironment","abstract":"// Maja Buszko 1 , Madalyn Jones 1 , Sruthi Chempati 1 , Lyra Morina 1 , Kirstin Ward 1 , Habtom Habte 2 , Michael Dziegielewski 2 and Ethan M. Shevach 1 1 Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, USA 2 Boehringer Ingelheim, Ridgefield, CT 06877, USA Correspondence to: Ethan M. Shevach, email: eshevach@Niaid.NIH.gov Keywords: T reg ; CD25; TME; mAb; GVHD Received: March 04, 2025     Accepted: June 16, 2025     Published: July 09, 2025 Copyright: © 2025 Buszko et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. ABSTRACT T reg play a deleterious role in the tumor microenvironment by suppressing anti-tumor effector T cells. Deletion of T reg can result in an enhanced anti-tumor response. It has been difficult to identify a cell surface antigen that is uniquely expressed on T reg which can be targeted by a deleting mAb. We immunized mice with human T reg cells which had been activated and expanded in vitro . One hybridoma (2B010) which recognized CD25 was identified. 2B010 demonstrated selective reactivity to T reg cells that had been expanded in culture for 5 days, but displayed similar reactivity to a conventional anti-CD25 mAb on freshly expanded T reg . 2B010 did not block the binding of IL-2 in the STAT5 phosphorylation assay and had no effect on the proliferation of T conv or on T reg suppressor function. It selectively reacted with T reg activated in vivo during xeno-GVHD and produced a selective deletion of T reg from mice undergoing xeno-GVHD. Administration of 2B010 to tumor bearing humanized mice resulted in a profound depletion of T reg from the TME and activation of CD8 + T cells. No effect on tumor growth was observed. 2B010 represents a candidate for treatment of patients with cancer either alone or together with check point inhibitors.","journal":"Oncotarget","year":2025,"id":569967,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9613,"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":1059976,"name":"Madalyn Jones","orcid":null,"position":1,"is_corresponding":false},{"id":1407229,"name":"Sruthi Chempati","orcid":"0009-0002-9608-8301","position":2,"is_corresponding":false},{"id":1059437,"name":"Lyra Morina","orcid":"0000-0002-7361-5407","position":3,"is_corresponding":false},{"id":1475443,"name":"Kirstin Ward","orcid":null,"position":4,"is_corresponding":false},{"id":1475444,"name":"Habtom H. Habte","orcid":null,"position":5,"is_corresponding":false},{"id":1475445,"name":"Michael Dziegielewski","orcid":null,"position":6,"is_corresponding":false},{"id":321383,"name":"Ethan M. Shevach","orcid":"0000-0003-1607-4664","position":7,"is_corresponding":false},{"id":385522,"name":"Maja Buszko","orcid":"0000-0002-8905-2223","position":0,"is_corresponding":true}],"reference_count":38,"raw_metadata":null,"created_at":"2026-07-19T02:57:03.510013Z","pmid":"40632611","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":[]}