Targeting therapy using a monoclonal antibody against tumor vascular endothelium

Recent studies have revealed that the targeting therapy using monoclonal an tibody against tumor associated antigens did not have a clinically satisfac tory effect due to various physiological characters of tumor. We propose a novel approach targeting tumor vascular endothelium to solve the inefficien cy of common tumor missile therapy. In this study, the tissue distribution of anti-tumor vascular endothelium monoclonal antibody (TES-23) produced by immunizing with plasma membrane vesicles obtained from isolated rat tumor- derived endothelial cells (TECs) was assessed in various tumor-bearing anim als. Radiolabeled TES-23 dramatically accumulated in KMT-17 fibrosarcoma, a source of isolated TECs after intravenous injection. In Meth-A fibrosarcom a, Colon-26 adenocarcinoma in BALB/c mice and HT-1080 human tumor tissue in nude mice, radioactivities of I-125-TES-23 were also up to fifty times hig her than those of control antibody with little distribution to normal tissu es. Furthermore, immunostaining of human tissue sections showed specific bi nding of TES-23 on endothelium in esophagus and colon cancers. These result s indicate that tumor vascular endothelial cells express a common antigen i n different tumor types of various animal species. In order to clarify the efficacy of TES-23 as a drug carrier, an immunoconjugate, composed of TES-2 3 and neocarzinostatin, was tested for its antitumor effect in vivo. The im munoconjugate (TES-23-NCS) caused a marked regression of the tumor, KMT-17 in rats and Meth-A in mice. Thus, from a clinical view, TES-23 would be a n ovel drug carrier because of its high specificity to tumor vascular endothe lium and its application to many types of cancer.