ABSTRACT
A major limitation in the chemotherapeutic treatment of cancer results from the lack of tumor specificity displayed by the drugs in use. One approach has been to prepare inactive drug precursors, known as prodrugs, that can be activated by enzymes or physiological conditions associated with cancer cells and tumor masses. Several drug targeting strategies are based on the preferential expression of a variety of antigens on tumor cell surfaces. The amount of active drug that can be delivered to tumors through a direct monoclonal antibodies (mAb)–drug conjugate is necessarily limited by the small amount of conjugate that localizes within human tumor masses. The strategy of using targeted enzymes for the generation of cytotoxic agents has been extended to include more conventional anticancer drugs. The potential utility of mAb–enzyme/prodrug therapy for the treatment of human cancers has been clearly demonstrated in a large number of in vivo therapeutic models.
