Chemotherapy of murine ovarian carcinoma by methotrexate-antibody conjugates

Abstract

Antibodies with specificity for an experimental ovarian carcinoma were coupled to methotrexate by 2 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 2 and conjugates of normal .gamma.-globulin with methotrexate. The 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.