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 antibody (TES-23) produced by immunizing with plasma membrane vesicles from isolated rat tumour-derived endothelial cells (TECs) was assessed in various tumour-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 125I-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 vivo. Furthermore, immunostaining of human tissue sections showed specific binding 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 of TES-23 as a drug carrier, an immunoconjugate, composed of TES-23 and neocarzinostatin, 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 view, 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.
Tsunoda
S
S
Department of Biopharmaceutics, School of Pharmaceutical Sciences, Osaka University, Suita, Japan.
Ohizumi
I
I
Matsui
J
J
Koizumi
K
K
Wakai
Y
Y
Makimoto
H
H
Tsutsumi
Y
Y
Utoguchi
N
N
Taniguchi
K
K
Saito
H
H
Harada
N
N
Ohsugi
Y
Y
Mayumi
T
T
D000230:Adenocarcinoma / Q000378:metabolism*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism*; D000918:Antibody Specificity; D000937:Antigen-Antibody Reactions; D004337:Drug Carriers; D016503:Drug Delivery Systems; D004730:Endothelium, Vascular / Q000276:immunology*; D005260:Female; D005354:Fibrosarcoma / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D051381:Rats; D014018:Tissue Distribution
D000911:Antibodies, Monoclonal; D004337:Drug Carriers