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M94A1927.TXT
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1994-10-24
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Document 1927
DOCN M94A1927
TI Binding ADCC and neutralization of primary HIV-1 isolates by high
affinity cross-linking of GP41 to human macrophage FC IGG receptor using
bispecific antibody.
DT 9412
AU Mabondzo A; Deo Y; Graziano R; Raoul H; Le Naour R; Romet-Lemonne JL;
Dormont D; SSA/DSV, CEA, Fontenay aux Roses, France.
SO Int Conf AIDS. 1994 Aug 7-12;10(1):42 (abstract no. 140A). Unique
Identifier : AIDSLINE ICA10/94370648
AB Human monocytes/macrophages, which express FcR for IgG are involved in
human immunodeficiency virus type 1 (HIV-1) infection pathogenesis.
These receptors are known to mediate numerous immunologic functions
including antibody mediating killing and possibly targeting of HIV to
lysophagosome monocytes/macrophages entry route which could lead to
virus neutralization. In an attempt to circumvent in vivo binding of
non-specific IgGs to Fc gamma RI which limit Fc gamma RI availability,
we report the development of chemical linked anti-Fc gamma RI x
anti-gp41 bispecific antibody which binds to an epitope outside the IgG
ligand binding site on Fc gamma RI. ELISA, immunofluorescence and flow
cytometry assays were used to determine binding the effect of bispecific
antibody to monocytes/macrophages in presence of various primary HIV
isolates and of HIV infected cells. Neutralizing capacity of bispecific
antibody compared to monoclonal antibody was assessed by measuring
reverse transcriptase activity and by quantification of unintegrated and
integrated viral DNA by PCR at several time points after infection of
various cell cultures. Killing activity of bispecific antibody against
infected targets cells was analyzed by 51 chromium release assay. Our
results demonstrate that the bispecific antibody binds and neutralizes a
variety of primary HIV-1 isolates. This viral inhibition occurs when
bispecific antibody binds to the Fc gamma RI, suggesting the successful
endocytosis through the Fc gamma RI pathway and intracellular
degradation. Furthermore, this bispecific antibody exhibits a potent
cytotoxicity against infected target cells. All results will be
discussed in context of therapeutic applications.
DE Antibodies, Bispecific/BIOSYNTHESIS/IMMUNOLOGY *Antibody Affinity
*Antibody-Dependent Cell Cytotoxicity Human HIV
Antibodies/*BIOSYNTHESIS HIV Envelope Protein gp41/*IMMUNOLOGY
HIV-1/*IMMUNOLOGY Macrophages/IMMUNOLOGY Receptors, IgG/IMMUNOLOGY
MEETING ABSTRACT
SOURCE: National Library of Medicine. NOTICE: This material may be
protected by Copyright Law (Title 17, U.S.Code).