A chimeric mouse-human antibody that retains specificity for HIV gp120 and mediates the lysis of HIV-infected cells.
Murine mAb BAT123, which was made against the envelope glycoprotein gp120 of HTLV-IIIB strain of HIV type 1 (HIV-1), is capable of neutralizing HTLV-IIIB in vitro. It also inhibits the fusion between uninfected CD4+ cells and HIV-1-infected cells to form syncytia. As a step to explore the potential utility of the anti-HIV antibody in vivo, we have constructed a mouse-human chimeric antibody by rDNA techniques. The chimeric antibody, which bears the variable domains of mouse antibody BAT123 and constant domains Cr1 and C kappa of human Ig retains the Ag specificity of BAT123 as determined by its reactivity with HIV-1-infected H9 cells, gp120 in Western blot analysis, and the oligopeptide recognized by BAT123. The antiviral activities of the chimeric antibody in neutralizing HIV-1 infection as well as inhibiting the syncytia formation are also found identical to those of the parent murine antibody. Moreover, in the presence of human blood mononuclear cells, the chimeric antibody but not BAT123 (mouse IgG1) induces antibody-dependent cellular cytotoxicity. The findings point to the potential usefulness of the chimeric antibody in treating patients infected with HIV-1.
Liou
R S
RS
Tanox Biosystems, Inc., Houston, TX 77025.
Rosen
E M
EM
Fung
M S
MS
Sun
W N
WN
Sun
C
C
Gordon
W
W
Chang
N T
NT
Chang
T W
TW
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis / Q000235:genetics* / Q000494:pharmacology; D000918:Antibody Specificity / Q000235:genetics*; D000920:Antibody-Dependent Cell Cytotoxicity; D001483:Base Sequence; D002678:Chimera; D000939:Epitopes / Q000032:analysis; D015686:Gene Products, env / Q000235:genetics / Q000276:immunology*; D015483:HIV Antibodies / Q000096:biosynthesis / Q000235:genetics / Q000302:isolation & purification; D015488:HIV Antigens / Q000276:immunology; D019302:HIV Envelope Protein gp160; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics / Q000302:isolation & purification; D007135:Immunoglobulin Variable Region / Q000235:genetics / Q000302:isolation & purification; D007145:Immunoglobulin kappa-Chains / Q000235:genetics* / Q000302:isolation & purification; D051379:Mice; D008969:Molecular Sequence Data; D011498:Protein Precursors / Q000235:genetics / Q000276:immunology*; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D000939:Epitopes; D015686:Gene Products, env; D015483:HIV Antibodies; D015488:HIV Antigens; D019302:HIV Envelope Protein gp160; D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; D007145:Immunoglobulin kappa-Chains; D011498:Protein Precursors; D011994:Recombinant Proteins