Tumor vascular targeting using a tumor-tissue endothelium-specific monoclonal antibody as an effective strategy for cancer chemotherapy.
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.
Department of Biopharmaceutics, School of Pharmaceutical Sciences, Osaka, 565-0871, Japan.
H
H
Makimoto
K
K
Koizumi
S
S
Tsunoda
Y
Y
Wakai
J
J
Matsui
Y
Y
Tsutsumi
S
S
Nakagawa
I
I
Ohizumi
K
K
Taniguchi
H
H
Saito
N
N
Utoguchi
Y
Y
Ohsugi
T
T
Mayumi
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000493:pharmacokinetics; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D004337:Drug Carriers; D004730:Endothelium, Vascular / Q000276:immunology*; D005260:Female; D051379:Mice; D009374:Neoplasms, Experimental / Q000188:drug therapy*; D051381:Rats; D014018:Tissue Distribution
D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D004337:Drug Carriers