{"doi":"10.1084/jem.20221166","title":"OX40L-expressing recombinant modified vaccinia virus Ankara induces potent antitumor immunity via reprogramming Tregs","abstract":"Effective depletion of immune suppressive regulatory T cells (Tregs) in the tumor microenvironment without triggering systemic autoimmunity is an important strategy for cancer immunotherapy. Modified vaccinia virus Ankara (MVA) is a highly attenuated, non-replicative vaccinia virus with a long history of human use. Here, we report rational engineering of an immune-activating recombinant MVA (rMVA, MVA∆E5R-Flt3L-OX40L) with deletion of the vaccinia E5R gene (encoding an inhibitor of the DNA sensor cyclic GMP-AMP synthase, cGAS) and expression of two membrane-anchored transgenes, Flt3L and OX40L. Intratumoral (IT) delivery of rMVA (MVA∆E5R-Flt3L-OX40L) generates potent antitumor immunity, dependent on CD8+ T cells, the cGAS/STING-mediated cytosolic DNA-sensing pathway, and type I IFN signaling. Remarkably, IT rMVA (MVA∆E5R-Flt3L-OX40L) depletes OX40hi regulatory T cells via OX40L/OX40 interaction and IFNAR signaling. Single-cell RNA-seq analyses of tumors treated with rMVA showed the depletion of OX40hiCCR8hi Tregs and expansion of IFN-responsive Tregs. Taken together, our study provides a proof-of-concept for depleting and reprogramming intratumoral Tregs via an immune-activating rMVA.","journal":"The Journal of Experimental Medicine","year":2023,"id":328614,"datarank":0.47670807455219194,"base_score":3.1780538303479458,"endowment":3.1780538303479458,"self_citation_contribution":0.47670807455219194,"citation_network_contribution":0.0,"self_endowment_contribution":0.47670807455219194,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":23,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9551,"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":573543,"name":"Yi Wang","orcid":"0000-0002-4046-9511","position":1,"is_corresponding":false},{"id":710313,"name":"Shuaitong Liu","orcid":"0000-0002-3695-1516","position":2,"is_corresponding":false},{"id":784093,"name":"Shanza Baseer Tariq","orcid":null,"position":3,"is_corresponding":false},{"id":228341,"name":"Joseph M. Luna","orcid":"0000-0003-2415-9203","position":4,"is_corresponding":false},{"id":281726,"name":"Gregory Mazo","orcid":"0000-0002-3877-1359","position":5,"is_corresponding":false},{"id":810005,"name":"Adrian Y. Tan","orcid":"0000-0001-6969-6606","position":6,"is_corresponding":false},{"id":109215,"name":"Tuo Zhang","orcid":"0000-0001-5396-918X","position":7,"is_corresponding":false},{"id":831448,"name":"Jiahu Wang","orcid":"0000-0003-1202-8724","position":8,"is_corresponding":false},{"id":1050528,"name":"Wei Yan","orcid":"0000-0002-2848-1155","position":9,"is_corresponding":false},{"id":831449,"name":"John Choi","orcid":"0009-0007-4567-6409","position":10,"is_corresponding":false},{"id":366935,"name":"Anthony Rossi","orcid":"0000-0003-2295-1934","position":11,"is_corresponding":false},{"id":109227,"name":"Jenny Xiang","orcid":"0000-0003-0484-2769","position":12,"is_corresponding":false},{"id":104737,"name":"Charles M. Rice","orcid":"0000-0003-3087-8079","position":13,"is_corresponding":false},{"id":109855,"name":"Taha Merghoub","orcid":"0000-0002-1518-5111","position":14,"is_corresponding":false},{"id":3666,"name":"Jedd D. Wolchok","orcid":"0000-0001-6718-2222","position":15,"is_corresponding":false},{"id":573544,"name":"Liang Deng","orcid":"0000-0002-8467-9342","position":16,"is_corresponding":false},{"id":573542,"name":"Ning Yang","orcid":"0000-0001-5121-7208","position":0,"is_corresponding":true}],"reference_count":58,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T01:08:56.940647Z","pmid":"37145142","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":[]}