{"doi":"10.1371/journal.ppat.1009831","title":"CAR/CXCR5-T cell immunotherapy is safe and potentially efficacious in promoting sustained remission of SIV infection","abstract":"During chronic human immunodeficiency virus (HIV) or simian immunodeficiency virus (SIV) infection prior to AIDS progression, the vast majority of viral replication is concentrated within B cell follicles of secondary lymphoid tissues. We investigated whether infusion of T cells expressing an SIV-specific chimeric antigen receptor (CAR) and the follicular homing receptor, CXCR5, could successfully kill viral-RNA+ cells in targeted lymphoid follicles in SIV-infected rhesus macaques. In this study, CD4 and CD8 T cells from rhesus macaques were genetically modified to express antiviral CAR and CXCR5 moieties (generating CAR/CXCR5-T cells) and autologously infused into a chronically infected animal. At 2 days post-treatment, the CAR/CXCR5-T cells were located primarily in spleen and lymph nodes both inside and outside of lymphoid follicles. Few CAR/CXCR5-T cells were detected in the ileum, rectum, and lung, and no cells were detected in the bone marrow, liver, or brain. Within follicles, CAR/CXCR5-T cells were found in direct contact with SIV-viral RNA+ cells. We next infused CAR/CXCR5-T cells into ART-suppressed SIV-infected rhesus macaques, in which the animals were released from ART at the time of infusion. These CAR/CXCR5-T cells replicated in vivo within both the extrafollicular and follicular regions of lymph nodes and accumulated within lymphoid follicles. CAR/CXR5-T cell concentrations in follicles peaked during the first week post-infusion but declined to undetectable levels after 2 to 4 weeks. Overall, CAR/CXCR5-T cell-treated animals maintained lower viral loads and follicular viral RNA levels than untreated control animals, and no outstanding adverse reactions were noted. These findings indicate that CAR/CXCR5-T cell treatment is safe and holds promise as a future treatment for the durable remission of HIV.","journal":"PLoS Pathogens","year":2022,"id":241173,"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":42,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9591,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":391274,"name":"Hadia M. Abdelaal","orcid":"0000-0002-1830-864X","position":1,"is_corresponding":false},{"id":275697,"name":"Emily K. Cartwright","orcid":"0000-0001-8644-0880","position":2,"is_corresponding":false},{"id":344038,"name":"Jhomary Molden","orcid":"0000-0001-6244-0827","position":3,"is_corresponding":false},{"id":344044,"name":"Brianna C. Davey","orcid":"0000-0001-5154-9077","position":4,"is_corresponding":false},{"id":809850,"name":"Jordan D. Sauve","orcid":null,"position":5,"is_corresponding":false},{"id":870554,"name":"Emily N. Sevcik","orcid":null,"position":6,"is_corresponding":false},{"id":375677,"name":"Aaron Rendahl","orcid":"0000-0001-5434-3592","position":7,"is_corresponding":false},{"id":286693,"name":"Eva G. Rakasz","orcid":"0000-0001-8197-5309","position":8,"is_corresponding":false},{"id":809384,"name":"Elizabeth Connick","orcid":"0000-0002-0465-6248","position":9,"is_corresponding":false},{"id":381836,"name":"Edward A. Berger","orcid":"0000-0001-8457-3997","position":10,"is_corresponding":false},{"id":344047,"name":"Pamela J. Skinner","orcid":"0000-0003-3388-1687","position":11,"is_corresponding":false},{"id":538036,"name":"Mary S. Pampusch","orcid":"0000-0002-6973-9474","position":0,"is_corresponding":true}],"reference_count":107,"raw_metadata":null,"created_at":"2026-07-19T00:22:56.227656Z","pmid":"35130312","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":[]}