Conjugated anti-TNF antibodies enhance the binding and degradation of TNF.
We have used disulfide-linked conjugates of murine anti-TNF antibodies to determine whether TNF binding to the cell surface could be increased by exploiting the Fc receptors present on monocytes and macrophages. Binding and degradation of TNF via Fc receptors may enhance the ability of anti-TNF antibodies to lower the high TNF levels found in several diseases. Conjugated murine anti-TNF antibodies greatly increased the binding of TNF to human U937 cells and had little effect on cells which did not express Fc receptors. U937 cells treated with anti-TNF conjugates also degraded more TNF than untreated cells. Competition analysis indicated that Fc receptors were involved in anti-TNF binding and that conjugated anti-TNF shared binding sites with monomeric anti-TNF. Preincubation of anti-TNF conjugates or monomeric anti-TNF with TNF increased the amount of anti-TNF antibody bound to the surface of cells. These results demonstrate that cross-linking may greatly enhance the ability of anti-TNF antibodies to mediate TNF clearance and degradation by making effective use of Fc receptors.
Lee
V W
VW
Cutter Biologicals Miles, Inc., Berkeley, California 94701.
Coan
M H
MH
Galloway
C J
CJ
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000936:Antigen-Antibody Complex; D001667:Binding, Competitive; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism*; D006801:Humans; D016403:Lymphoma, Large B-Cell, Diffuse / Q000378:metabolism*; D051379:Mice; D011961:Receptors, Fc / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D011961:Receptors, Fc; D014409:Tumor Necrosis Factor-alpha