Binding kinetics, uptake and intracellular accumulation of F105, an anti-gp120 human IgG1kappa monoclonal antibody, in HIV-1 infected cells.
The use of targeting moieties is a new and exciting field of scientific research for facilitating the specific delivery of therapeutic agents in HIV-infected patients. The interaction of a potential targeting moiety with its ligand is a crucial factor in the evaluation of a targeted approach for chemotherapeutic intervention. Therefore, we have further characterized the interaction between a potential targeting agent, the monoclonal human antibody F105, and its ligand gp120, a glycoprotein expressed on the surface of HIV-1 infected cells. We demonstrate the specificity of binding and entry of F105 to infected cells. F105 was rapidly taken up into the cell and accumulated in the Golgi apparatus. Kinetic analysis of the F105-gp120 interaction revealed an equilibrium dissociation constant (K(D)) of 0.62 nM, compared with the gp120-CD4 interaction where the K(D) was determined at 35 nM. Consequently, F105 displayed a higher gp120 affinity. This was due to a slower dissociation as compared with the natural ligand. These data further underline the potential of monoclonal antibodies as targeting agents, and offer new insights into the possibility of F105 as a targeting moiety for the delivery of antiretroviral drugs to HIV-1 infected cells.
Clayton
Reginald
R
Tibotec BVBA, Generaal De Wittelaan L 11B 3, 2800 Mechelen, Belgium. rclayton@tibbe.jnj.com
Ohagen
Asa
A
Goethals
Olivia
O
Smets
Alexandra
A
Van Loock
Marnix
M
Michiels
Lieve
L
Kennedy-Johnston
Erin
E
Cunningham
Mark
M
Jiang
Haiyan
H
Bola
Sharon
S
Gutshall
Lester
L
Gunn
George
G
Del Vecchio
Alfred
A
Sarisky
Robert
R
Hallenberger
Sabine
S
Hertogs
Kurt
K
D000163:Acquired Immunodeficiency Syndrome / Q000628:therapy*; D000911:Antibodies, Monoclonal / Q000378:metabolism* / Q000627:therapeutic use; D015699:HIV Envelope Protein gp120 / Q000276:immunology*; D015497:HIV-1; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism*; D007145:Immunoglobulin kappa-Chains / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D015699:HIV Envelope Protein gp120; D007074:Immunoglobulin G; D007145:Immunoglobulin kappa-Chains