{"doi":"10.1371/journal.ppat.1011853","title":"Chimeric antigen receptors enable superior control of HIV replication by rapidly killing infected cells","abstract":"Engineered T cells hold great promise to become part of an effective HIV cure strategy, but it is currently unclear how best to redirect T cells to target HIV. To gain insight, we generated engineered T cells using lentiviral vectors encoding one of three distinct HIV-specific T cell receptors (TCRs) or a previously optimized HIV-targeting chimeric antigen receptor (CAR) and compared their functional capabilities. All engineered T cells had robust, antigen-specific polyfunctional cytokine profiles when mixed with artificial antigen-presenting cells. However, only the CAR T cells could potently control HIV replication. TCR affinity enhancement did not augment HIV control but did allow TCR T cells to recognize common HIV escape variants. Interestingly, either altering Nef activity or adding additional target epitopes into the HIV genome bolstered TCR T cell anti-HIV activity, but CAR T cells remained superior in their ability to control HIV replication. To better understand why CAR T cells control HIV replication better than TCR T cells, we performed a time course to determine when HIV-specific T cells were first able to activate Caspase 3 in HIV-infected targets. We demonstrated that CAR T cells recognized and killed HIV-infected targets more rapidly than TCR T cells, which correlates with their ability to control HIV replication. These studies suggest that the speed of target recognition and killing is a key determinant of whether engineered T cell therapies will be effective against infectious diseases.","journal":"PLoS Pathogens","year":2023,"id":361497,"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":9,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9476,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":487254,"name":"Julie K. Jadlowsky","orcid":"0009-0005-5115-1321","position":1,"is_corresponding":false},{"id":1114241,"name":"Caitlin Baiduc","orcid":null,"position":2,"is_corresponding":false},{"id":1114242,"name":"Alex W. Klattenhoff","orcid":null,"position":3,"is_corresponding":false},{"id":639194,"name":"Zhilin Chen","orcid":"0000-0003-4594-2731","position":4,"is_corresponding":false},{"id":1113769,"name":"Alan Bennett","orcid":"0000-0003-0942-7425","position":5,"is_corresponding":false},{"id":1114243,"name":"Nicholas J. Pumphrey","orcid":null,"position":6,"is_corresponding":false},{"id":1114244,"name":"Bent K. Jakobsen","orcid":null,"position":7,"is_corresponding":false},{"id":263033,"name":"James L. Riley","orcid":"0000-0002-1057-576X","position":8,"is_corresponding":false},{"id":487253,"name":"Yuqi Zhou","orcid":"0009-0009-5656-8475","position":0,"is_corresponding":true}],"reference_count":91,"raw_metadata":null,"created_at":"2026-07-19T01:14:10.680991Z","pmid":"38100526","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":[]}