{"doi":"10.1126/science.adl4237","title":"Programming tissue-sensing T cells that deliver therapies to the brain","abstract":"To engineer cells that can specifically target the central nervous system (CNS), we identified extracellular CNS-specific antigens, including components of the CNS extracellular matrix and surface molecules expressed on neurons or glial cells. Synthetic Notch receptors engineered to detect these antigens were used to program T cells to induce the expression of diverse payloads only in the brain. CNS-targeted T cells that induced chimeric antigen receptor expression efficiently cleared primary and secondary brain tumors without harming cross-reactive cells outside of the brain. Conversely, CNS-targeted cells that locally delivered the immunosuppressive cytokine interleukin-10 ameliorated symptoms in a mouse model of neuroinflammation. Tissue-sensing cells represent a strategy for addressing diverse disorders in an anatomically targeted manner.","journal":"Science","year":2024,"id":417147,"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":80,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9507,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":271182,"name":"Payal Watchmaker","orcid":"0000-0002-0944-3890","position":1,"is_corresponding":false},{"id":703299,"name":"Sasha Gupta","orcid":"0000-0002-1972-7301","position":2,"is_corresponding":false},{"id":288643,"name":"Yuan Wang","orcid":"0000-0001-7750-3587","position":3,"is_corresponding":false},{"id":805146,"name":"Sharon A. Sagan","orcid":"0009-0008-2212-5783","position":4,"is_corresponding":false},{"id":615944,"name":"Jason Duecker","orcid":"0000-0002-4978-0867","position":5,"is_corresponding":false},{"id":962234,"name":"Chanelle Shepherd","orcid":"0009-0007-9958-5043","position":6,"is_corresponding":false},{"id":748179,"name":"David Diebold","orcid":"0000-0002-6857-767X","position":7,"is_corresponding":false},{"id":915290,"name":"Psalm Pineo-Cavanaugh","orcid":"0000-0002-1521-1607","position":8,"is_corresponding":false},{"id":1203365,"name":"Jeffrey Haegelin","orcid":null,"position":9,"is_corresponding":false},{"id":1202567,"name":"Robert Zhu","orcid":"0000-0001-6477-2497","position":10,"is_corresponding":false},{"id":1202568,"name":"Ben Ng","orcid":"0000-0003-4418-5054","position":11,"is_corresponding":false},{"id":256490,"name":"Wei Yu","orcid":"0000-0002-3154-5084","position":12,"is_corresponding":false},{"id":625097,"name":"Yurie Tonai","orcid":"0000-0001-9610-6667","position":13,"is_corresponding":false},{"id":615945,"name":"Lia Cardarelli","orcid":"0000-0002-2516-0188","position":14,"is_corresponding":false},{"id":578707,"name":"Nishith R. Reddy","orcid":"0000-0001-5912-6925","position":15,"is_corresponding":false},{"id":227344,"name":"Sachdev S. Sidhu","orcid":"0000-0001-7755-5918","position":16,"is_corresponding":false},{"id":5951,"name":"Olga G. Troyanskaya","orcid":"0000-0002-5676-5737","position":17,"is_corresponding":false},{"id":246852,"name":"Stephen L. Hauser","orcid":"0000-0002-4932-4001","position":18,"is_corresponding":false},{"id":109296,"name":"Michael R. Wilson","orcid":"0000-0002-8705-5084","position":19,"is_corresponding":false},{"id":246282,"name":"Scott S. Zamvil","orcid":"0000-0003-2720-9915","position":20,"is_corresponding":false},{"id":271186,"name":"Hideho Okada","orcid":"0000-0003-0076-9920","position":21,"is_corresponding":false},{"id":256019,"name":"Wendell A. Lim","orcid":"0000-0003-4052-8056","position":22,"is_corresponding":false},{"id":615939,"name":"Milos Simic","orcid":"0000-0002-1167-0857","position":0,"is_corresponding":true}],"reference_count":65,"raw_metadata":null,"created_at":"2026-07-19T01:56:50.743370Z","pmid":"39636984","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":[]}