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.