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Tumor vascular targeting using a tumor-tissue endothelium-specific monoclonal antibody as an effective strategy for
H Makimoto1, K Koizumi, S Tsunoda
1Department of Biopharmaceutics, School of Pharmaceutical Sciences, Osaka, 565-0871, Japan.
Abstract:
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.
Insights
Researchers developed a novel tumor vascular targeting agent, TES-23-NCS, by conjugating a monoclonal antibody with Neocarzinostatin (NCS). This targeted therapy demonstrated significant anti-tumor effects on KMT-17 tumors without side effects, indicating potential for broad cancer treatment.
Area of Science:
- Oncology
- Immunology
- Pharmacology
Background:
- Tumor vascular targeting offers a strategy to selectively deliver anti-cancer agents.
- Monoclonal antibodies can be engineered to target tumor-specific endothelial cells.
- Neocarzinostatin (NCS) is a potent anti-tumor antibiotic requiring targeted delivery.
Purpose of the Study:
- To develop and evaluate a tumor vascular targeting agent using a tumor tissue endothelium-specific antibody.
- To assess the anti-tumor efficacy and safety of the immunoconjugate TES-23-NCS.
Main Methods:
- Chemical conjugation of the monoclonal antibody TES-23 with Neocarzinostatin (NCS).
- In vivo evaluation of anti-tumor activity in KMT-17 tumor-bearing rats and Sarcoma-180 tumor-bearing mice.
- Tissue distribution analysis of TES-23 and TES-23-NCS.
Main Results:
- TES-23-NCS exhibited significant anti-tumor effects on KMT-17 tumors, inducing hemorrhagic necrosis at a low dose (17 µg/kg NCS equivalent) without side effects.
- Control groups (TES-23 alone, NCS alone, Mopc-NCS) showed no significant anti-tumor activity.
- High accumulation of TES-23 and TES-23-NCS was observed in KMT-17 tumors within 1 hour of intravenous administration.
- TES-23 also showed accumulation in Sarcoma-180 tumors, suggesting broad applicability.
Conclusions:
- TES-23-NCS demonstrates potent and specific anti-tumor activity through tumor vascular targeting.
- The antibody TES-23 shows promise as a targeting agent for various tumor types.
- This approach offers a potential strategy for effective cancer therapy with reduced systemic toxicity.