{"doi":"10.1172/jci.insight.161698","title":"In vivo killing of primary HIV-infected cells by peripheral-injected early memory–enriched anti-HIV duoCAR T cells","abstract":"HIV-specific chimeric antigen receptor-T cell (CAR T cell) therapies are candidates to functionally cure HIV infection in people with HIV (PWH) by eliminating reactivated HIV-infected cells derived from latently infected cells within the HIV reservoir. Paramount to translating such therapeutic candidates successfully into the clinic will require anti-HIV CAR T cells to localize to lymphoid tissues in the body and eliminate reactivated HIV-infected cells such as CD4+ T cells and monocytes/macrophages. Here we show that i.v. injected anti-HIV duoCAR T cells, generated using a clinical-grade anti-HIV duoCAR lentiviral vector, localized to the site of active HIV infection in the spleen of humanized mice and eliminated HIV-infected PBMCs. CyTOF analysis of preinfusion duoCAR T cells revealed an early memory phenotype composed predominantly of CCR7+ stem cell-like/central memory T cells (TSCM/TCM) with expression of some effector-like molecules. In addition, we show that anti-HIV duoCAR T cells effectively sense and kill HIV-infected CD4+ T cells and monocytes/macrophages. Furthermore, we demonstrate efficient genetic modification of T cells from PWH on suppressive ART into anti-HIV duoCAR T cells that subsequently kill autologous PBMCs superinfected with HIV. These studies support the safety and efficacy of anti-HIV duoCAR T cell therapy in our presently open phase I/IIa clinical trial (NCT04648046).","journal":"JCI Insight","year":2022,"id":240083,"datarank":1.0831977264614445,"base_score":3.8712010109078907,"endowment":3.8712010109078907,"self_citation_contribution":0.5806801516361837,"citation_network_contribution":0.5025175748252608,"self_endowment_contribution":0.5806801516361837,"citer_contribution":0.5025175748252608,"corpus_percentile":null,"corpus_rank":null,"citation_count":47,"citer_count":41,"citers_with_citation_signal":31,"citers_with_endowment":31,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9498,"is_data_producer":true,"deposit_databanks":{"ClinicalTrials.gov":["NCT04648046"]},"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":379058,"name":"Alex Ray","orcid":"0000-0001-5760-7821","position":1,"is_corresponding":false},{"id":388571,"name":"Hang Su","orcid":"0000-0002-3726-2771","position":2,"is_corresponding":false},{"id":867130,"name":"Yuge Wang","orcid":"0000-0003-3005-6163","position":3,"is_corresponding":false},{"id":459394,"name":"Ying Xiong","orcid":"0000-0001-7412-1727","position":4,"is_corresponding":false},{"id":712032,"name":"Danica Lee","orcid":"0000-0003-3871-8061","position":5,"is_corresponding":false},{"id":867971,"name":"Ariele Block","orcid":null,"position":6,"is_corresponding":false},{"id":693293,"name":"Vanessa Chilunda","orcid":null,"position":7,"is_corresponding":false},{"id":867131,"name":"Jessica Weiselberg","orcid":"0000-0003-0455-7407","position":8,"is_corresponding":false},{"id":867972,"name":"Lily Zemelko","orcid":null,"position":9,"is_corresponding":false},{"id":855464,"name":"Yen Y. 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