Specific binding of TES-23 antibody to tumour vascular endothelium in mice, rats and human cancer tissue: a novel drug carrier for cancer targeting therapy

The tissue distribution of anti-tumour vascular endothelium monoclonal anti body (TES-23) produced by immunizing with plasma membrane vesicles from iso lated rat tumour-derived endothelial cells (TECs) was assessed in various t umour-bearing animals. Radiolabelled TES-23 dramatically accumulated in KMT -17 fibrosarcoma, the source of isolated TECs after intravenous injection. in Meth-A fibrosarcoma, Colon-26 adenocarcinoma in BALB/c mice and HT-1080 human tumour tissue in nude mice, radioactivities of I-125-labelled TES-23 were also up to 50 times higher than those of control antibody with little distribution to normal tissues. The selective recognition of TES-23 to TECs was competitively blocked by preadministration of unlabelled TES-23 in viv o. Furthermore, immunostaining of human tissue sections showed specific bin ding of TES-23 on endothelium in oesophagus cancers. These results indicate that tumour vascular endothelial cells express common antigen in different tumour types of various animal species. In order to clarify the efficacy o f TES-23 as a drug carrier, an immunoconjugate, composed of TES-23 and neoc arzinostatin, was tested for its anti-tumour effect in rats bearing KMT-17 fibrosarcomas. The immunoconjugate (TES-23-NCS) caused marked regression of the tumour, accompanied by haemorrhagic necrosis. Thus, from a clinical vi ew, TES-23 would be a novel drug carrier because of its high specificity to tumour vascular endothelium and its application to many types of cancer. ( C) 1999 Cancer Research Campaign.