{"doi":"10.1016/j.xcrm.2025.102198","title":"Immune targeting of triple-negative breast cancer through a clinically actionable STING agonist-CAR T cell platform","abstract":"Stimulator of interferon genes (STING) has emerged as a critical cancer immunotherapy target. However, no STING agonist has advanced beyond phase I/II clinical trials, as obstacles center around applying STING agonism to the appropriate clinical context, retaining it in the tumor microenvironment (TME), and limiting its T cell toxicity. Using triple-negative breast cancer (TNBC), we identify defective STING turnover as a cancer state promoting hypersensitivity to STING agonism. We also repurpose a US Food and Drug Administration (FDA)-approved polyethylene glycol (PEG) biopsy marker to deliver STING agonists in a controlled release fashion into the TME. However, STING agonist-induced T cell toxicity limits robust endogenous clonal T cell response, which can be overcome by sequential co-delivery of the STING agonists with CAR T cell therapy using the same PEG marker, eradicating orthotopic TNBC in mouse models while also controlling distant disease. These findings identify a highly translatable platform to combine STING agonists with CAR T cell therapy locally for TNBC and potentially other solid cancers.","journal":"Cell Reports Medicine","year":2025,"id":531543,"datarank":0.24141568686511508,"base_score":1.6094379124341003,"endowment":1.6094379124341003,"self_citation_contribution":0.24141568686511508,"citation_network_contribution":0.0,"self_endowment_contribution":0.24141568686511508,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9617,"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":851566,"name":"Zehua Li","orcid":"0000-0001-6342-3324","position":1,"is_corresponding":false},{"id":849660,"name":"Jessica Ritter","orcid":"0000-0001-7106-7518","position":2,"is_corresponding":false},{"id":1411779,"name":"Elliott J. Brea","orcid":"0000-0002-6283-0267","position":3,"is_corresponding":false},{"id":38303,"name":"Navin R. Mahadevan","orcid":"0000-0002-6805-8861","position":4,"is_corresponding":false},{"id":74572,"name":"Deborah Dillon","orcid":"0000-0002-4977-6673","position":5,"is_corresponding":false},{"id":318828,"name":"Sung-Rye Park","orcid":null,"position":6,"is_corresponding":false},{"id":13129,"name":"Eric Minwei Liu","orcid":"0000-0002-3594-6678","position":7,"is_corresponding":false},{"id":23418,"name":"Michael Tolstorukov","orcid":"0000-0002-9134-8808","position":8,"is_corresponding":false},{"id":1412276,"name":"William E McGourty","orcid":null,"position":9,"is_corresponding":false},{"id":227598,"name":"Patrick H. Lizotte","orcid":"0000-0001-9510-0036","position":10,"is_corresponding":false},{"id":269864,"name":"Elena V. Ivanova","orcid":"0000-0002-5069-4974","position":11,"is_corresponding":false},{"id":1052332,"name":"Caroline Fahey","orcid":null,"position":12,"is_corresponding":false},{"id":849659,"name":"Koji Haratani","orcid":"0000-0002-1767-6854","position":13,"is_corresponding":false},{"id":227609,"name":"Tran C. Thai","orcid":"0000-0003-4799-0876","position":14,"is_corresponding":false},{"id":253239,"name":"Kara M. Soroko","orcid":null,"position":15,"is_corresponding":false},{"id":849664,"name":"Sophie Kivlehan","orcid":"0000-0002-5672-1697","position":16,"is_corresponding":false},{"id":243187,"name":"Eric L. Smith","orcid":"0000-0002-0296-7587","position":17,"is_corresponding":false},{"id":30766,"name":"Prafulla C. Gokhale","orcid":"0000-0002-1974-5921","position":18,"is_corresponding":false},{"id":227616,"name":"Cloud P. Paweletz","orcid":"0000-0002-2287-5663","position":19,"is_corresponding":false},{"id":227617,"name":"David A. Barbie","orcid":"0000-0002-5422-4275","position":20,"is_corresponding":false},{"id":461746,"name":"Thanh U. Barbie","orcid":"0000-0002-2187-0801","position":21,"is_corresponding":false},{"id":903870,"name":"Yu‐Qing Zhang","orcid":"0000-0001-7670-386X","position":0,"is_corresponding":true}],"reference_count":72,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:51:14.579161Z","pmid":"40543510","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":[]}