A conjugate of alpha-amanitin and monoclonal immunoglobulin G to Thy 1.2 antigen is selectively toxic to T lymphoma cells.
A covalent conjugate of an alpha-amanitin azo derivative and a monoclonal immunoglobulin G to the Thy 1.2 antigen on murine T lymphocytes was synthesized. The conjugate was 375- to 750-fold more inhibitory to murine T lymphoma S49.1 cells than the unconjugated derivative. At 0.7 X 10(-7) to 1.5 X 10(-7) M and at 4 X 10(-7) M amanitin equivalents, the conjugate inhibited protein synthesis in S49.1 cells by 50 percent and 80 to 96 percent, respectively. At these concentrations, mutant Thy l-deficient S49 cells and other murine lymphoma lacking Thy l altogether or carrying Thy 1.1 antigens were unaffected. This result demonstrated the potential for targeting amanitin to specific cell types.
D000546:Amanitins / Q000008:administration & dosage*; D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D000906:Antibodies / Q000008:administration & dosage; D000911:Antibodies, Monoclonal; D000954:Antigens, Surface / Q000276:immunology*; D002478:Cells, Cultured; D002999:Clone Cells / Q000276:immunology; D006822:Hybrid Cells / Q000276:immunology; D007074:Immunoglobulin G / Q000008:administration & dosage*; D008223:Lymphoma / Q000188:drug therapy*; D008565:Membrane Proteins / Q000276:immunology*; D051379:Mice; D009374:Neoplasms, Experimental / Q000188:drug therapy; D013601:T-Lymphocytes / Q000187:drug effects; D018800:Thy-1 Antigens
D000546:Amanitins; D000596:Amino Acids; D000906:Antibodies; D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D007074:Immunoglobulin G; D008565:Membrane Proteins; D018800:Thy-1 Antigens