Biological properties of a CD4 immunoadhesin.
Molecular fusions of CD4, the receptor for human immunodeficiency virus (HIV), with immunoglobulin (termed CD4 immunoadhesins) possess both the gp120-binding and HIV-blocking properties of recombinant soluble CD4, and certain properties of IgG, notably long plasma half-life and Fc receptor binding. Here we show that a CD4 immunoadhesin can mediate antibody-dependent cell-mediated cytotoxicity (ADCC) towards HIV-infected cells, although, unlike natural anti-gp120 antibodies, it does not allow ADCC towards uninfected CD4-expressing cells that have bound soluble gp120 to the CD4 on their surface. In addition, CD4 immunoadhesin, like natural IgG molecules, is efficiently transferred across the placenta of a primate. These observations have implications for the therapeutic application of CD4 immunoadhesins, particularly in the area of perinatal transmission of HIV infection.
Byrn
R A
RA
Genentech Inc., South San Francisco, California 94080.
Mordenti
J
J
Lucas
C
C
Smith
D
D
Marsters
S A
SA
Johnson
J S
JS
Cossum
P
P
Chamow
S M
SM
Wurm
F M
FM
Gregory
T
T
Groopman
J E
JE
Capon
D J
DJ
D000163:Acquired Immunodeficiency Syndrome / Q000151:congenital / Q000276:immunology; D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology*; D000920:Antibody-Dependent Cell Cytotoxicity / Q000276:immunology; D015703:Antigens, CD / Q000276:immunology*; D016860:CD4 Immunoadhesins; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000382:microbiology; D005260:Female; D006678:HIV / Q000276:immunology*; D015699:HIV Envelope Protein gp120 / Q000276:immunology; D006801:Humans; D007112:Immunity, Maternally-Acquired; D007074:Immunoglobulin G / Q000276:immunology*; D008253:Macaca mulatta; D011247:Pregnancy; D011994:Recombinant Proteins
D000888:Antibodies, Anti-Idiotypic; D015703:Antigens, CD; D016860:CD4 Immunoadhesins; D015699:HIV Envelope Protein gp120; D007074:Immunoglobulin G; D011994:Recombinant Proteins