Effective cancer targeting using an anti-tumor tissue vascular endothelium-specific monoclonal antibody (TES-23).
Immunoconjugate targeting of solid tumors has not been routinely successful because the endo-thelial cells of blood vessels act as a physical barrier against the transport of macromolecules, such as antibodies. In the present study, we attempted to achieve tumor vascular targeting with an anti-tumor tissue endothelium-specific monoclonal antibody (TES-23). TES-23, an IgG1 monoclonal antibody raised against rat KMT-17 fibrosarcoma-derived endothelial cells, was covalently conjugated with neocarzinostatin (NCS) in a previous study. The TES-23-NCS conjugate induced tumor hemorrhagic necrosis, and showed marked anti-tumor effects against rat KMT-17 fibrosarcoma. This result prompted us to investigate whether this approach would be applicable to various other types of solid tumors. One hour after injection of (125)I-labeled TES-23 into BALB / c mice bearing Meth-A fibrosarcoma and Colon 26 adenocarcinoma, the tumor accumulation of TES-23 was greater than that of the control IgG. In the present study, we report the anti-tumor effects of this monoclonal antibody in mice bearing Meth-A fibrosarcoma. Mice treated with the immunoconjugate showed improved survival with no side effects. This result indicates that common antigens may be found in different kinds of tumor endothelial cells, and that TES-23 might recognize these antigens.
Wakai
Y
Y
Department of Biopharmaceutics, School of Pharmaceutical Sciences, Osaka University, Suita, Osaka 565-0871, Japan. mayumi@phs.osaka-u.ac.jp
Matsui
J
J
Koizumi
K
K
Tsunoda
S
S
Makimoto
H
H
Ohizumi
I
I
Taniguchi
K
K
Kaiho
S
S
Saito
H
H
Utoguchi
N
N
Tsutsumi
Y
Y
Nakagawa
S
S
Ohsugi
Y
Y
Mayumi
T
T
D000818:Animals; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000918:Antibody Specificity; D001835:Body Weight; D004730:Endothelium, Vascular / Q000276:immunology*; D005260:Female; D005354:Fibrosarcoma / Q000098:blood supply / Q000188:drug therapy* / Q000532:radiotherapy*; D006470:Hemorrhage; D007074:Immunoglobulin G; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics / Q000627:therapeutic use*; D051379:Mice; D008807:Mice, Inbred BALB C; D009336:Necrosis; D016499:Radioimmunotherapy / Q000379:methods; D051381:Rats; D014018:Tissue Distribution; D009353:Zinostatin / Q000493:pharmacokinetics / Q000627:therapeutic use*
D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D007457:Iodine Radioisotopes; D009353:Zinostatin