Simultaneous interaction of monoclonal antibody-targeted liposomes with two receptors on K562 cells.
We have investigated the interaction of targeted liposomes with human erythrocytes, and K562 cells, a human leukemic line which expresses both glycophorin A and Fc receptors. Liposomes conjugated to monoclonal anti-human glycophorin A bind to human erythrocytes in 80-fold greater amounts than liposomes conjugated to a non-specific monoclonal antibody. Binding is inhibited by soluble anti-glycophorin but not by its Fab fragment. In contrast, binding of antibody-conjugated liposomes to K562 cells is very high irrespective of the specificity of the antibody. Liposomes conjugated to a nonspecific monoclonal antibody interact with K562 cells via an Fc receptor, and binding is inhibited by soluble human IgG. Liposomes conjugated to anti-human glycophorin A interact with K562 cells via an Fc receptor and glycophorin A. Binding is not inhibited by either human IgG or anti-glycophorin Fab alone. Binding is only partially inhibited by anti-glycophorin, or by human IgG in the presence of anti-glycophorin Fab, and completely inhibited only by human IgG in the presence of anti-glycophorin. Simultaneous binding of targeted liposomes to two cell membrane antigens is therefore partially resistant to inhibition by single soluble ligands even when they are present in large excess. We conclude that simultaneous binding to more than one receptor may be of considerable advantage for in vivo applications of targeted liposomes.
D000911:Antibodies, Monoclonal; D002460:Cell Line; D004912:Erythrocytes / Q000378:metabolism*; D006021:Glycophorins / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000378:metabolism; D015470:Leukemia, Myeloid, Acute / Q000378:metabolism*; D008081:Liposomes / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000276:immunology*; D011961:Receptors, Fc / Q000378:metabolism*; D017452:Receptors, IgG; D012795:Sialoglycoproteins / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D006021:Glycophorins; D007140:Immunoglobulin Fab Fragments; D008081:Liposomes; D011956:Receptors, Cell Surface; D011961:Receptors, Fc; D017452:Receptors, IgG; D012795:Sialoglycoproteins