Bispecific antibodies promote natural killer cell-mediated elimination of HIV-1 reservoir cells.

Autor: Board NL; Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD, USA., Yuan Z; The Wistar Institute, Philadelphia, PA, USA., Wu F; Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD, USA., Moskovljevic M; Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD, USA., Ravi M; Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD, USA., Sengupta S; Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD, USA., Mun SS; Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD, USA., Simonetti FR; Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD, USA., Lai J; Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD, USA., Tebas P; Presbyterian Hospital-University of Pennsylvania Hospital, Philadelphia, PA, USA., Lynn K; Presbyterian Hospital-University of Pennsylvania Hospital, Philadelphia, PA, USA., Hoh R; Department of Medicine, University of California San Francisco, San Francisco, CA, USA., Deeks SG; Department of Medicine, University of California San Francisco, San Francisco, CA, USA., Siliciano JD; Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD, USA. jsilicia@jhmi.edu., Montaner LJ; The Wistar Institute, Philadelphia, PA, USA. montaner@wistar.org., Siliciano RF; Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD, USA. rsiliciano@jhmi.edu.; Howard Hughes Medical Institute, Baltimore, MD, USA. rsiliciano@jhmi.edu.
Jazyk: angličtina
Zdroj: Nature immunology [Nat Immunol] 2024 Mar; Vol. 25 (3), pp. 462-470. Date of Electronic Publication: 2024 Jan 26.
DOI: 10.1038/s41590-023-01741-5
Abstrakt: The persistence of CD4 + T cells carrying latent human immunodeficiency virus-1 (HIV-1) proviruses is the main barrier to a cure. New therapeutics to enhance HIV-1-specific immune responses and clear infected cells will probably be necessary to achieve reduction of the latent reservoir. In the present study, we report two single-chain diabodies (scDbs) that target the HIV-1 envelope protein (Env) and the human type III Fcγ receptor (CD16). We show that the scDbs promoted robust and HIV-1-specific natural killer (NK) cell activation and NK cell-mediated lysis of infected cells. Cocultures of CD4 + T cells from people with HIV-1 on antiretroviral therapy (ART) with autologous NK cells and the scDbs resulted in marked elimination of reservoir cells that was dependent on latency reversal. Treatment of human interleukin-15 transgenic NSG mice with one of the scDbs after ART initiation enhanced NK cell activity and reduced reservoir size. Thus, HIV-1-specific scDbs merit further evaluation as potential therapeutics for clearance of the latent reservoir.
(© 2024. The Author(s).)
Databáze: MEDLINE
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