Target ricin by coupling to an anti-macrophage monoclonal antibody.
By altering the receptor binding specificity of the highly potent natural toxin ricin, a macrophage specific immunotoxin was developed. Ricin ordinarily does not demonstrate cell type specificity and is capable of binding and entering cells through galactose containing receptors resulting in rapid cell death. A murine anti-rat peritoneal macrophage IgGl monoclonal antibody, B-6, was developed to serve as a target specific carrier for ricin. By covalently binding monoclonal antibody B-6 and reversibly binding lactose to ricin, a new biologically active hybrid toxin possessing macrophage specificity was developed. When P3X63-Ag8.653 myeloma cells, which served as an nonspecific target cell type, and macrophages were treated with the ricin conjugate over a broad range of concentrations and various time periods, the conjugate demonstrated substantially greater toxicity toward macrophages than myeloma cells even though both cell types responded similarly to treatments with unconjugated ricin. It was also observed that ricin was considerably more toxic to macrophages when conjugated to monoclonal antibody B-6 than unconjugated ricin. Through ricin-antibody conjugation a high degree of specificity and toxicity can be attained potentially suitable for anti-tumor reagents and immuno-modulators.
D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis / Q000627:therapeutic use* / Q000633:toxicity; D001402:B-Lymphocytes / Q000276:immunology; D001666:Binding Sites, Antibody; D002470:Cell Survival / Q000187:drug effects; D003429:Cross Reactions; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D005779:Immunodiffusion; D008264:Macrophages / Q000187:drug effects / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009101:Multiple Myeloma / Q000188:drug therapy; D051381:Rats; D011919:Rats, Inbred Strains; D011961:Receptors, Fc / Q000276:immunology; D012276:Ricin / Q000494:pharmacology* / Q000633:toxicity; D013601:T-Lymphocytes / Q000276:immunology
D000911:Antibodies, Monoclonal; D011961:Receptors, Fc; D012276:Ricin