title: Targeted lysis of HIV-infected cells by natural killer cells armed and triggered by a recombinant immunoglobulin fusion protein: implications for immunotherapy.
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.
authors.affiliation: Laboratory of Immunoregulation, NIAID, NIH Bldg. #10 6A08, 9000 Rockville Pike, Bethesda MD 20892, USA.
authors.forename: Neil
authors.initials: N
authors.lastname: Gupta
authors.forename: James
authors.initials: J
authors.lastname: Arthos
authors.forename: Prateeti
authors.initials: P
authors.lastname: Khazanie
authors.forename: Tavis D
authors.initials: TD
authors.lastname: Steenbeke
authors.forename: Nina M
authors.initials: NM
authors.lastname: Censoplano
authors.forename: Eva A
authors.initials: EA
authors.lastname: Chung
authors.forename: Catherine C
authors.initials: CC
authors.lastname: Cruz
authors.forename: Margery A
authors.initials: MA
authors.lastname: Chaikin
authors.forename: Marybeth
authors.initials: M
authors.lastname: Daucher
authors.forename: Shyam
authors.initials: S
authors.lastname: Kottilil
authors.forename: Domenico
authors.initials: D
authors.lastname: Mavilio
authors.forename: Peter
authors.initials: P
authors.lastname: Schuck
authors.forename: Peter D
authors.initials: PD
authors.lastname: Sun
authors.forename: Ronald L
authors.initials: RL
authors.lastname: Rabin
authors.forename: Sergei
authors.initials: S
authors.lastname: Radaev
authors.forename: Donald
authors.initials: D
authors.lastname: Van Ryk
authors.forename: Claudia
authors.initials: C
authors.lastname: Cicala
authors.forename: Anthony S
authors.initials: AS
authors.lastname: Fauci
mesh_terms: D000920:Antibody-Dependent Cell Cytotoxicity; D015703:Antigens, CD / Q000276:immunology; D020013:Calcium Signaling / Q000502:physiology; D045744:Cell Line, Tumor; D005434:Flow Cytometry; D015658:HIV Infections / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D007167:Immunotherapy / Q000379:methods; D007694:Killer Cells, Natural / Q000276:immunology*; D017452:Receptors, IgG / Q000276:immunology
chemical_list: D015703:Antigens, CD; D007074:Immunoglobulin G; D017452:Receptors, IgG