Tumor vascular targeting using a tumor-tissue endothelium-specific monoclonal antibody as an effective strategy for cancer chemotherapy.

Abstract

In this study, we attempted to develop tumor vascular targeting with a tumor tissue endothelium-specific monoclonal antibody. TES-23, which strongly and selectively recognizes tumor tissue endothelial cells, was chemically conjugated with Neocarzinostatin (NCS), and the anti-tumor effect was examined. The immunoconjugate, TES-23-NCS, showed, through the use of tumor hemorrhagic necrosis, a marked anti-tumor effect on KMT-17 tumors in rats at a dosage of 17 micrograms/kg (NCS equivalent) without any side effects, probably due to specific tumor vascular injury. By contrast, TES-23 alone (107 micrograms/kg), NCS alone (17 micrograms/kg), and Mopc-NCS (Mopc, 107 micrograms/kg; NCS, 17 micrograms/kg), the immunoconjugate of control antibody, did not have any anti-tumor activities. By tissue distribution analysis, TES-23 and TES-23-NCS showed high accumulation in KMT-17 tumors 1 h after intravenous administration. Moreover TES-23 also accumulated in Sarcoma-180 tumors in mice 1 h after intravenous administration. These results suggest that TES-23 may be a candidate for a potential tumor vascular targeting agent that is applicable to a wide variety of tumor types.

• Authors: H Makimoto, K Koizumi, S Tsunoda, Y Wakai, J Matsui, Y Tsutsumi, S Nakagawa, I Ohizumi, K Taniguchi, H Saito, N Utoguchi, Y Ohsugi, T Mayumi
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 260 Issue 2 Pg. 346-50 (Jul 05 1999) ISSN: 0006-291X [Print] United States
• PMID: 10403773 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 1999 Academic Press.

Chemical References

• Antibodies, Monoclonal
• Antineoplastic Agents
• Drug Carriers

Topics

• Animals
• Antibodies, Monoclonal (immunology, pharmacokinetics)
• Antineoplastic Agents (administration & dosage, pharmacokinetics, therapeutic use)
• Drug Carriers
• Endothelium, Vascular (immunology)
• Female
• Mice
• Neoplasms, Experimental (drug therapy)
• Rats
• Tissue Distribution