Targeted lysis of HIV-infected cells by natural killer cells armed and triggered by a recombinant immunoglobulin fusion protein: implications for immunotherapy.
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.
Gupta
Neil
N
Laboratory of Immunoregulation, NIAID, NIH Bldg. #10 6A08, 9000 Rockville Pike, Bethesda MD 20892, USA.
Arthos
James
J
Khazanie
Prateeti
P
Steenbeke
Tavis D
TD
Censoplano
Nina M
NM
Chung
Eva A
EA
Cruz
Catherine C
CC
Chaikin
Margery A
MA
Daucher
Marybeth
M
Kottilil
Shyam
S
Mavilio
Domenico
D
Schuck
Peter
P
Sun
Peter D
PD
Rabin
Ronald L
RL
Radaev
Sergei
S
Van Ryk
Donald
D
Cicala
Claudia
C
Fauci
Anthony S
AS
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
D015703:Antigens, CD; D007074:Immunoglobulin G; D017452:Receptors, IgG