This paper describes chemical modification of the toxic agent Leucinostatin A and its conjugation with a monoclonal antibody. The molecule, isolated from a culture filtrate of Paecilomyces marquandii (Massee) Hughes, is a nonapeptide antibiotic with cytotoxic and phytotoxic properties. To evaluate its toxicity, and to improve its specificity as an antitumor agent, the molecule was conjugated to the monoclonal antibody AR-3, specific to human colorectal and ovarian carcinomas. The targeting ability of AR-3, bearing different amounts of toxic agent, was tested on related and unrelated cell lines. Stability of the ester linkage between Leucinostatin A and AR-3 was also studied. In this study we show that coupling of Leucinostatin A with a tumor-directed monoclonal antibody is a practical way to increase both the cytotoxicity and selectivity of the chemotherapeutic agent.
Antibody-targeted leucinostatin A.
RICCI, Maurizio;ROSSI, Carlo;
1994
Abstract
This paper describes chemical modification of the toxic agent Leucinostatin A and its conjugation with a monoclonal antibody. The molecule, isolated from a culture filtrate of Paecilomyces marquandii (Massee) Hughes, is a nonapeptide antibiotic with cytotoxic and phytotoxic properties. To evaluate its toxicity, and to improve its specificity as an antitumor agent, the molecule was conjugated to the monoclonal antibody AR-3, specific to human colorectal and ovarian carcinomas. The targeting ability of AR-3, bearing different amounts of toxic agent, was tested on related and unrelated cell lines. Stability of the ester linkage between Leucinostatin A and AR-3 was also studied. In this study we show that coupling of Leucinostatin A with a tumor-directed monoclonal antibody is a practical way to increase both the cytotoxicity and selectivity of the chemotherapeutic agent.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
