Polymer modification of antibody to eliminate immune complex and Fc binding.
Antibodies are currently being explored as highly specific reagents for delivering toxins, drugs or radionuclides to a variety of cell populations including tumors. These in vitro and in vivo antibody techniques are however associated with several problems which must be overcome prior to the routine therapeutic or diagnostic use of antibody reagents. One of the major problems is that cellular Fc receptors can interfere with the specificity of binding. This report describes the use of covalent modification with monomethoxypolyethylene glycol as a method to suppress Fc binding and other non-specific interactions of antibody molecules. The results demonstrate that modification of less than 20% of an antibodies exposed lysine residues with the polymer eliminates Fc-dependent binding to a murine macrophage cell line and prevents non-specific and Fc-dependent binding of fluoresceinated antibodies to mouse splenocytes.
D000818:Animals; D000888:Antibodies, Anti-Idiotypic; D000936:Antigen-Antibody Complex / Q000378:metabolism*; D001666:Binding Sites, Antibody / Q000187:drug effects*; D001667:Binding, Competitive; D003207:Conalbumin / Q000276:immunology; D016650:Fluorescein-5-isothiocyanate; D005452:Fluoresceins; D051379:Mice; D011092:Polyethylene Glycols / Q000494:pharmacology*; D011108:Polymers / Q000494:pharmacology*; D011817:Rabbits; D011961:Receptors, Fc / Q000187:drug effects / Q000378:metabolism*; D013154:Spleen / Q000166:cytology; D013861:Thiocyanates
D000888:Antibodies, Anti-Idiotypic; D000936:Antigen-Antibody Complex; D005452:Fluoresceins; D011108:Polymers; D011961:Receptors, Fc; D013861:Thiocyanates; D003207:Conalbumin; D011092:Polyethylene Glycols; C028210:monomethoxypolyethylene glycol; D016650:Fluorescein-5-isothiocyanate