ANTIBODY-TARGETED LEUCINOSTATIN-A

This paper describes chemical modification of the toxic agent Leucinos tatin A and its conjugation with a monoclonal antibody. The molecule, isolated from a culture filtrate of Paecilomyces marquandii (Massee) H ughes, is a nonapeptide antibiotic with cytotoxic and phytotoxic prope rties. To evaluate its toxicity, and to improve its specificity as an antitumor agent, the molecule was conjugated to the monoclonal antibod y AR-3, specific to human colorectal and ovarian carcinomas. The targe ting ability of AR-3, bearing different amounts of toxic agent, was te sted on related and unrelated cell lines. Stability of the eater linka ge between Leucinostatin A and AR-3 was also studied. In this study we show that coupling of Leucinostatin A with a tumor-directed monoclona l antibody is a practical way to increase both the cytotoxicity and se lectivity of the chemotherapeutic agent.