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).