Functional activities of 20 human immunodeficiency virus type 1 (HIV-1)-specific human monoclonal antibodies.
Antibodies that are useful in the treatment of HIV infection should result in virus neutralization or lysis of infected cells but should not enhance infection. In this study, the potential clinical use of 20 HIV-1-specific human monoclonal antibodies (HuMAbs) was determined by measuring their enhancing (C-ADE) activities using HIVLAI as the target virus. Two HuMAbs mediated both C-ADE and ADCC, two exclusively neutralized, and five exclusively mediated ADCC. Ten HuMAbs demonstrated no activity in any of the three assays. Three antibodies that neutralized HIVLAI were tested against HIVSF2; all three also neutralized HIVSF2. Four of five HuMAbs mediating ADCC against HIVLAI that were also tested against HIVSF2 had ADCC activity against HIVSF2. These results demonstrate that many HuMAbs have unique functions, allowing the separation of potentially beneficial and harmful activities. Combinations of HuMAbs with ADCC and neutralizing functions may have therapeutic utility.
Forthal
D N
DN
Department of Medicine, University of California, Irvine College of Medicine, Orange 92668, USA.
Landucci
G
G
Gorny
M K
MK
Zolla-Pazner
S
S
Robinson
W E
WE
D000911:Antibodies, Monoclonal / Q000494:pharmacology* / Q000627:therapeutic use; D000918:Antibody Specificity; D000920:Antibody-Dependent Cell Cytotoxicity; D002460:Cell Line; D003165:Complement System Proteins / Q000378:metabolism; D015483:HIV Antibodies / Q000494:pharmacology* / Q000627:therapeutic use; D015658:HIV Infections / Q000276:immunology / Q000628:therapy; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D009500:Neutralization Tests
D000911:Antibodies, Monoclonal; D015483:HIV Antibodies; D003165:Complement System Proteins