Chemotherapy of murine ovarian carcinoma by methotrexate-antibody conjugates.
Antibodies with specificity for an experimental ovarian carcinoma were coupled to methotrexate by two procedures. Water-soluble carbodiimide gave effective coupling, but a large proportion of the conjugate was rendered insoluble, presumably due to alteration or aggregation of the antibodies. A modification of the mixed anhydride procedure gave rise to products which were completely soluble and allowed a high degree of coupling to be achieved. In vivo testing of the conjugates revealed a significant increase in survival time in treated mice when compared to a variety of control groups; these included groups receiving antiserum or drug alone, mixtures of the two, and conjugates of normal gamma-globulin with methotrexate. Our results provide added support for the concept that tumor-associated antibodies coupled to cytotoxic agents are more effective than single agents or noncoupled mixtures of agents.
D000812:Anhydrides / Q000276:immunology; D000818:Animals; D000912:Antibodies, Neoplasm / Q000008:administration & dosage*; D000918:Antibody Specificity; D005260:Female; D008727:Methotrexate / Q000008:administration & dosage / Q000627:therapeutic use*; D051379:Mice; D008809:Mice, Inbred C3H; D009374:Neoplasms, Experimental / Q000188:drug therapy; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D011817:Rabbits / Q000276:immunology; D013997:Time Factors; D005719:gamma-Globulins
D000812:Anhydrides; D000912:Antibodies, Neoplasm; D005719:gamma-Globulins; D008727:Methotrexate