Radiosensitizer conjugation to the carcinoma 19-9 monoclonal antibody.
Misonidazole was covalently conjugated (3-68 mol drug/mol antibody) to 19-9 monoclonal antibody directed against a colorectal carcinoma tumor-associated antigen as a method for targeting radiosensitizing agents. This attachment was accomplished by the mixed anhydride method using the hemisuccinate derivative of misonidazole. Evaluation of conjugates in vitro shows a loss of antibody binding activity with increasing loading levels; however, significant binding activity is retained even at relatively high sensitizer/antibody ratios. This observation was consistent in three binding assays: a competitive radioimmunoassay; an enzyme immunoassay; and an affinity column assay. From these studies, it was concluded that the optimal loading factor for misonidazole-antibody conjugates, when it is used for immunochemotherapy lies between 8 and 15. In vitro release studies indicated that conjugates are hydrolytically stable (t1/2 = 4 days) under physiological conditions.
D000911:Antibodies, Monoclonal / Q000276:immunology; D000912:Antibodies, Neoplasm / Q000276:immunology; D000937:Antigen-Antibody Reactions; D000951:Antigens, Neoplasm / Q000276:immunology*; D015295:Antigens, Tumor-Associated, Carbohydrate; D002846:Chromatography, Affinity; D003110:Colonic Neoplasms / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D007074:Immunoglobulin G / Q000276:immunology; D000922:Immunotoxins / Q000138:chemical synthesis; D008920:Misonidazole; D011863:Radioimmunoassay; D012004:Rectal Neoplasms / Q000276:immunology
D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm; D000951:Antigens, Neoplasm; D015295:Antigens, Tumor-Associated, Carbohydrate; D007074:Immunoglobulin G; D000922:Immunotoxins; D008920:Misonidazole