ARTICLE: Bispecific antibodies promote natural killer cell-mediated elimination of HIV-1 reservoir cells
AUTHORS: Nathan L Board, Zhe Yuan, Fengting Wu, Milica Moskovljevic, Meghana Ravi, Srona Sengupta, Sung Soo Mun, Francesco R Simonetti, Jun Lai, Pablo Tebas, Kenneth Lynn, Rebecca Hoh, Steven G Deeks, Janet D Siliciano, Luis J Montaner, Robert F Siliciano
JOURNAL: Nat Immunol. 2024 Jan 26. doi: 10.1038/s41590-023-01741-5. Online ahead of print.
Abstract
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.
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