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Virology 2005 Feb 20;332(2):491-7

Targeted lysis of HIV-infected cells by natural killer cells armed and triggered by a recombinant immunoglobulin fusion protein: implications for immunotherapy.

Gupta N, Arthos J, Khazanie P, Steenbeke TD, Censoplano NM, Chung EA, Cruz CC, Chaikin MA, Daucher M, Kottilil S, Mavilio D, Schuck P, Sun PD, Rabin RL, Radaev S, Van Ryk D, Cicala C, Fauci AS

Arthos J, NIAID, Immunoregulat Lab, NIH, Bldg 10 6A08,9000 Rockville Pike, Bethesda, MD 20892 USA NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA NIH, Prot Biophys Resource, DPBS, ORS, Bethesda, MD 20892 USA NIAID, Immunogenet Lab, NIH, Bethesda, MD 20892 USA US FDA, Div Bacterial Parasit & Allergen Prod, CBER, Bethesda, MD 20892 USA

Abstract

Natural killer (NK) cells play an important role in both innate and adaptive antiviral immune responses. The adaptive response typically requires that virus-specific antibodies decorate infected cells which then direct NK cell lysis through a CD16 mediated process termed antibody-dependent cellular cytotoxicity (ADCC). In this report, we employ a highly polymerized chimeric IgG1/IgA immunoglobulin (Ig) fusion protein that, by virtue of its capacity to extensively crosslink CD16, activates NK cells while directing the lysis of infected target cells. We employ HIV as a model system, and demonstrate that freshly isolated NK cells preloaded with an HIV gp120-specific chimeric IgG1/IgA fusion protein efficiently lyse HIV-infected target cells at picomolar concentrations. NK cells pre-armed in this manner retain the capacity to kill targets over an extended period of time. This strategy may have application to other disease states including various viral infections and cancers.


Category: Journal Article, Peer
PubMed ID: #15680414
Includes FDA Authors from Scientific Area(s): Biologics
Entry Created: 2011-10-04 Entry Last Modified: 2012-08-29
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