{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T14:23:16Z","timestamp":1778682196436,"version":"3.51.4"},"reference-count":91,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T00:00:00Z","timestamp":1778198400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    Despite significant advances in antiretroviral therapy (ART), human immunodeficiency virus (HIV) persists in long-lived viral reservoirs, requiring lifelong treatment and highlighting the need for curative strategies. Viral persistence across anatomically distinct reservoirs, together with HIV-associated immune dysregulation, supports the development of combination immunotherapies capable of acting through multiple antiviral mechanisms. Here, we developed and evaluated a Hybrid chimeric antigen receptor (CAR) platform that combines the targeted cytotoxicity of CAR-T cells with the secretion of broadly neutralizing antibodies (bNAbs). We assessed the capacity of Hybrid CAR-T cells to eliminate HIV-infected cells, neutralize free virus, and recruit Fc-mediated effector mechanisms\n                    <jats:italic>in vitro<\/jats:italic>\n                    , and evaluated their antiviral activity in humanized mice.\n                    <jats:italic>In vitro<\/jats:italic>\n                    , Hybrid CAR-T cells eliminated HIV-infected CD4+ T cells, while secreted bNAbs neutralized HIV and mediated robust Fc-effector functions, including antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP). In humanized mice, Hybrid CAR-T treatment achieved more than a 9-fold reduction in plasma viremia, accompanied by a significant decrease in viral levels across tissues and detectable circulating bNAbs in plasma. Collectively, these findings demonstrate that Hybrid CAR-T cells can bridge cellular and humoral immunity by combining direct killing of HIV-infected cells with antibody-mediated antiviral activity. This dual-function platform represents a synergistic next-generation immunotherapy with translational potential as a strategy toward a functional HIV cure.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2026.1822773","type":"journal-article","created":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T05:54:34Z","timestamp":1778219674000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Broadly neutralizing antibody-secreting CAR-T cells elicit Fc-mediated effector functions in vitro and suppress HIV in humanized mice"],"prefix":"10.3389","volume":"17","author":[{"given":"Zoe","family":"Stylianidou","sequence":"first","affiliation":[{"name":"HIV Cure Research Center, Department of Internal Medicine and Pediatrics, Faculty of Medicine and Health Sciences, University of Ghent","place":["Ghent, 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University of Ghent","place":["Ghent, Belgium"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Evelien","family":"De Smet","sequence":"additional","affiliation":[{"name":"HIV Cure Research Center, Department of Internal Medicine and Pediatrics, Faculty of Medicine and Health Sciences, University of Ghent","place":["Ghent, Belgium"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ytse","family":"Noppe","sequence":"additional","affiliation":[{"name":"HIV Cure Research Center, Department of Internal Medicine and Pediatrics, Faculty of Medicine and Health Sciences, University of Ghent","place":["Ghent, Belgium"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maxime","family":"Verschoore","sequence":"additional","affiliation":[{"name":"HIV Cure Research Center, Department of Internal Medicine and Pediatrics, Faculty of Medicine and Health Sciences, University of Ghent","place":["Ghent, 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