{"doi":"10.1016/j.omtm.2020.04.024","title":"Preclinical Development and Clinical-Scale Manufacturing of HIV Gag-Specific, LentivirusModified CD4 T Cells for HIV Functional Cure","abstract":"Activation, infection, and eventual depletion of human immunodeficiency virus (HIV)-specific cluster of differentiation 4 (CD4) T cells are the crucial pathogenetic events in acquired immunodeficiency syndrome (AIDS). We developed a cell and gene therapy to reconstitute HIV-specific CD4 T cells and prevent their destruction by HIV. Antigen-specific CD4 T cells will provide helper functions to support antiviral cytotoxic T lymphocyte (CTL) function and the production of virus-specific antibodies. However, ex vivo expansion of HIV-specific CD4 T cells is poor and previous gene therapies focused on bulk CD4 T cells without enriching for an antigen-specific subset. We developed a method for manufacturing autologous CD4+ T cell products highly enriched with Gag-specific T cells. Rare Gag-specific CD4 T cells in peripheral blood mononuclear cells (PBMCs) were increased nearly 1,000-fold by stimulating PBMC with Gag peptides, followed by depleting nontarget cells and transducing with lentivirus vector AGT103 to protect against HIV-mediated depletion and inhibit HIV release from latently infected cells. The average percentage of HIV-specific CD4 cells in the final products was 15.13%, and the average yield was 7 × 108 cells. The protocol for clinical-scale manufacturing of HIV-specific and HIV-resistant CD4 T cells is an important step toward effective immunotherapy for HIV disease. Activation, infection, and eventual depletion of human immunodeficiency virus (HIV)-specific cluster of differentiation 4 (CD4) T cells are the crucial pathogenetic events in acquired immunodeficiency syndrome (AIDS). We developed a cell and gene therapy to reconstitute HIV-specific CD4 T cells and prevent their destruction by HIV. Antigen-specific CD4 T cells will provide helper functions to support antiviral cytotoxic T lymphocyte (CTL) function and the production of virus-specific antibodies. However, ex vivo expansion of HIV-specific CD4 T cells is poor and previous gene therapies focused on bulk CD4 T cells without enriching for an antigen-specific subset. We developed a method for manufacturing autologous CD4+ T cell products highly enriched with Gag-specific T cells. Rare Gag-specific CD4 T cells in peripheral blood mononuclear cells (PBMCs) were increased nearly 1,000-fold by stimulating PBMC with Gag peptides, followed by depleting nontarget cells and transducing with lentivirus vector AGT103 to protect against HIV-mediated depletion and inhibit HIV release from latently infected cells. The average percentage of HIV-specific CD4 cells in the final products was 15.13%, and the average yield was 7 × 108 cells. The protocol for clinical-scale manufacturing of HIV-specific and HIV-resistant CD4 T cells is an important step toward effective immunotherapy for HIV disease.","journal":"Molecular Therapy — Methods & Clinical Development","year":2020,"id":73980,"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":12,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9575,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":389246,"name":"Tyler Lahusen","orcid":null,"position":1,"is_corresponding":false},{"id":389247,"name":"Lingzhi Xiao","orcid":null,"position":2,"is_corresponding":false},{"id":389248,"name":"Nidal Muvarak","orcid":null,"position":3,"is_corresponding":false},{"id":387593,"name":"Jana Blažková","orcid":"0000-0002-6000-202X","position":4,"is_corresponding":false},{"id":228710,"name":"Tae‐Wook Chun","orcid":"0000-0001-5153-7340","position":5,"is_corresponding":false},{"id":387594,"name":"C. David Pauza","orcid":"0000-0002-0559-793X","position":6,"is_corresponding":false},{"id":387584,"name":"Haishan Li","orcid":"0000-0002-9577-277X","position":0,"is_corresponding":true}],"reference_count":50,"raw_metadata":null,"created_at":"2026-07-18T21:45:52.171053Z","pmid":"32462053","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":[]}