{"doi":"10.1172/jci141051","title":"T cell receptor–targeted immunotherapeutics drive selective in vivo HIV- and CMV-specific T cell expansion in humanized mice","abstract":"To delineate the in vivo role of different costimulatory signals in activating and expanding highly functional virus-specific cytotoxic CD8+ T cells, we designed synTacs, infusible biologics that recapitulate antigen-specific T cell activation signals delivered by antigen-presenting cells. We constructed synTacs consisting of dimeric Fc-domain scaffolds linking CD28- or 4-1BB-specific ligands to HLA-A2 MHC molecules covalently tethered to HIV- or CMV-derived peptides. Treatment of HIV-infected donor PBMCs with synTacs bearing HIV- or CMV-derived peptides induced vigorous and selective ex vivo expansion of highly functional HIV- and/or CMV-specific CD8+ T cells, respectively, with potent antiviral activities. Intravenous injection of HIV- or CMV-specific synTacs into immunodeficient mice intrasplenically engrafted with donor PBMCs markedly and selectively expanded HIV-specific (32-fold) or CMV-specific (46-fold) human CD8+ T cells populating their spleens. Notably, these expanded HIV- or CMV-specific CD8+ T cells directed potent in vivo suppression of HIV or CMV infections in the humanized mice, providing strong rationale for consideration of synTac-based approaches as a therapeutic strategy to cure HIV and treat CMV and other viral infections. The synTac platform flexibility supports facile delineation of in vivo effects of different costimulatory signals on patient-derived virus-specific CD8+ T cells, enabling optimization of individualized therapies, including HIV cure strategies.","journal":"Journal of Clinical Investigation","year":2021,"id":173831,"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":24,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9501,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":230344,"name":"S. Garforth","orcid":"0000-0001-6281-4833","position":1,"is_corresponding":false},{"id":712577,"name":"Kaitlyn E. O’Connor","orcid":null,"position":2,"is_corresponding":false},{"id":388571,"name":"Hang Su","orcid":"0000-0002-3726-2771","position":3,"is_corresponding":false},{"id":712032,"name":"Danica Lee","orcid":"0000-0003-3871-8061","position":4,"is_corresponding":false},{"id":552490,"name":"A. Celikgil","orcid":"0000-0001-8760-4496","position":5,"is_corresponding":false},{"id":712033,"name":"Rodolfo Chaparro","orcid":"0000-0001-7000-8022","position":6,"is_corresponding":false},{"id":475733,"name":"R.D. Seidel","orcid":"0000-0003-1265-7993","position":7,"is_corresponding":false},{"id":95313,"name":"R. Brad Jones","orcid":"0000-0003-4470-1231","position":8,"is_corresponding":false},{"id":422618,"name":"Ravit Arav‐Boger","orcid":"0000-0002-5363-167X","position":9,"is_corresponding":false},{"id":230350,"name":"Steven C. Almo","orcid":"0000-0003-2591-5234","position":10,"is_corresponding":false},{"id":409944,"name":"Harris Goldstein","orcid":"0000-0003-0543-6025","position":11,"is_corresponding":false},{"id":712031,"name":"Mengyan Li","orcid":"0000-0002-1635-3674","position":0,"is_corresponding":true}],"reference_count":69,"raw_metadata":null,"created_at":"2026-07-18T23:46:49.903770Z","pmid":"34673568","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":[]}