{"doi":"10.1128/jvi.01933-24","title":"Persistence of CMV-specific anti-HIV CAR T cells after adoptive immunotherapy","abstract":"ABSTRACT The success of chimeric antigen receptor (CAR)-T cell (Tc) immunotherapy in refractory B-cell acute lymphoblastic leukemia (B-ALL) suggests adaptation of this strategy toward HIV. Because cytomegalovirus (CMV) vaccine vectors generated Tc responses that controlled viral replication, these studies aim to genetically modify CMV-specific Tc with HIV-CAR2 vectors and link HIV immunotherapy to persistent CMV antigen stimulation. To mimic a clinical scenario, rhesus macaques were challenged with the CCR5-tropic simian/human immunodeficiency virus (SHIV-D) prior to antiretroviral therapy (ART). Autologous CMV-specific Tc were transduced with the control CEA-CAR2 or CD4-CAR2/maC46 vectors and reinfused. After stopping ART, the plasma viral load (PVL) in the control rebounded and was sustained above 1.7 × 10 4 copies/mL; PVL in CD4-CAR2-treated animals was delayed up to 6 weeks and 10-fold lower. The CD4 CAR-Tc frequency peaked at day 7 and was detected in lymphoid tissues at 6 weeks. Both CEA-CAR2 and CD4-CAR2 persisted in PBMCs for about 2 years, which indicates that the CMV-specific CAR Tc were maintained based on their CMV specificity. However, long-term PVL was stable in all animals. Thus, CMV-specific CAR-Tc were active initially, persisted long term, but failed to control viral replication. IMPORTANCE Because of latent viral reservoirs and a dysfunctional immune response, HIV replication rebounds when antiretroviral therapy is interrupted. Therefore, cytomegalovirus (CMV)-specific Tc were genetically modified with anti-HIV CD4-CAR2 vectors to link the targeting of the HIV envelope to the persistent CMV immune response. In this clinical scenario with simian/human immunodeficiency virus (SHIV) challenge and antiretroviral therapy (ART) suppression, early activity of the CAR Tc delayed rebound in the rhesus macaque/SHIV challenge model. However, even with long-term persistence of CAR Tc in the blood, control of viral replication was not achieved. These data suggest that CAR Tc will require additional interventions to cure HIV infection.","journal":"Journal of Virology","year":2025,"id":528105,"datarank":0.16479184330021646,"base_score":1.0986122886681096,"endowment":1.0986122886681096,"self_citation_contribution":0.16479184330021646,"citation_network_contribution":0.0,"self_endowment_contribution":0.16479184330021646,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9519,"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":579697,"name":"Nathan M. Johnson","orcid":"0000-0001-7994-9523","position":1,"is_corresponding":false},{"id":849157,"name":"Yu Shan","orcid":"0000-0002-8165-8407","position":2,"is_corresponding":false},{"id":759562,"name":"Agnes S. Lo","orcid":"0000-0002-1673-7619","position":3,"is_corresponding":false},{"id":1406131,"name":"Gautam K. Sahu","orcid":null,"position":4,"is_corresponding":false},{"id":343913,"name":"Preston A. Marx","orcid":"0000-0002-6955-2511","position":5,"is_corresponding":false},{"id":576171,"name":"Dorotheé von Laer","orcid":"0000-0001-5825-7237","position":6,"is_corresponding":false},{"id":1406132,"name":"Gail Skowron","orcid":null,"position":7,"is_corresponding":false},{"id":353338,"name":"Romas Geleziunas","orcid":"0000-0002-9290-8811","position":8,"is_corresponding":false},{"id":253820,"name":"George M. Shaw","orcid":"0000-0002-2338-4532","position":9,"is_corresponding":false},{"id":422425,"name":"Amitinder Kaur","orcid":"0000-0001-6609-4896","position":10,"is_corresponding":false},{"id":303528,"name":"Richard P. Junghans","orcid":null,"position":11,"is_corresponding":false},{"id":442097,"name":"Stephen E. Braun","orcid":"0000-0002-4521-2678","position":12,"is_corresponding":false},{"id":789084,"name":"Chengxiang Wu","orcid":"0000-0002-6184-187X","position":0,"is_corresponding":true}],"reference_count":53,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:50:44.062153Z","pmid":"40207929","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":[]}