{"doi":"10.1093/jimmun/vkaf283.299","title":"VirTac, a modular lentiviral-based platform, elicits selective and marked expansion of HIV-, CMV- and SARS-CoV-2-specific T cell responses, validating its applications for adoptive T cell therapies 2374","abstract":"Abstract Description New strategies to efficiently generate virus- and cancer-specific CD8 T cells are needed to increase antigenic breadth, efficacy and use of adoptive T-cell therapies for infectious diseases and cancer. We developed VirTac (VT), a modular lentivirus (LV)-based non-infectious immunotherapeutic platform to mimic features of APCs by presenting membrane proteins that elicit the selective expansion of antigen-specific CD8 T cells. We demonstrate that VT bearing single chain HLA-A*0201 MHC constructs presenting SL9 (HIV), NLV (CMV) or YLQ (CoV-2) peptides, either alone or combined with an agonist αCD28 scFv, can selectively modulate antigen-specific CD8 T cells. In vitro treatment of human donor PBMCs (n = 2-5) with SL9-, NLV- or YLQ-VT markedly expanded CD8 T cell populations specific for HIV (>20%), CMV (>87%) or CoV2 (>67%), respectively. Intravenous infusion of VT into NSG mice expanded HIV- and CMV-specific T cells by ∼30-fold; this response was enhanced in some of these donors by inclusion of the agonist αCD28 scFv in the VT. Antigen-specific T cells expanded with VT displayed potent antigen-specific cytotoxic activity, IFNγ and TNFα production and suppression of in vitro HIV or CMV infections. VT represents a highly modular platform that drives robust and selective ex vivo and in vivo expansion of antigen-specific CD8 T cells and enables diverse applications for enhancing adoptive cellular therapies to treat infectious diseases, autoimmune diseases and oncology indications. Funding Sources NIH R01 AI145024; NIH R01AI172607; NIH P30 AI124414 Topic Categories Vaccines and Immunotherapy (VAC)","journal":"The Journal of Immunology","year":2025,"id":582410,"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":0.9555,"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":515333,"name":"Erin L. Cole","orcid":"0009-0000-6486-4340","position":1,"is_corresponding":false},{"id":454352,"name":"April L. Mueller","orcid":"0000-0002-2134-5134","position":2,"is_corresponding":false},{"id":1215447,"name":"Christopher Hiner","orcid":null,"position":3,"is_corresponding":false},{"id":1494487,"name":"Agnes Syndenstricker","orcid":null,"position":4,"is_corresponding":false},{"id":1494488,"name":"Adilyn Voss","orcid":null,"position":5,"is_corresponding":false},{"id":1036774,"name":"Jian Hua","orcid":"0000-0002-3777-3344","position":6,"is_corresponding":false},{"id":230344,"name":"S. Garforth","orcid":"0000-0001-6281-4833","position":7,"is_corresponding":false},{"id":230350,"name":"Steven C. Almo","orcid":"0000-0003-2591-5234","position":8,"is_corresponding":false},{"id":409944,"name":"Harris Goldstein","orcid":"0000-0003-0543-6025","position":9,"is_corresponding":false},{"id":1494106,"name":"Marta Santos Bravo","orcid":"0000-0001-5270-4454","position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-19T02:58:55.657290Z","pmid":null,"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":[]}