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[Targeting therapy using a monoclonal antibody against tumor vascular endothelium]
S Tsunoda1, Y Tsutsumi, S Nakagawa
1School of Pharmaceutical Sciences, Osaka University, Japan.
Abstract:
Recent studies have revealed that the targeting therapy using monoclonal antibody against tumor associated antigens did not have a clinically satisfactory effect due to various physiological characters of tumor. We propose a novel approach targeting tumor vascular endothelium to solve the inefficiency of common tumor missile therapy. In this study, the tissue distribution of anti-tumor vascular endothelium monoclonal antibody (TES-23) produced by immunizing with plasma membrane vesicles obtained from isolated rat tumor-derived endothelial cells (TECs) was assessed in various tumor-bearing animals. Radiolabeled TES-23 dramatically accumulated in KMT-17 fibrosarcoma, a source of isolated TECs after intravenous injection. In Meth-A fibrosarcoma, Colon-26 adenocarcinoma in BALB/c mice and HT-1080 human tumor tissue in nude mice, radioactivities of 125I-TES-23 were also up to fifty times higher than those of control antibody with little distribution to normal tissues. Furthermore, immunostaining of human tissue sections showed specific binding of TES-23 on endothelium in esophagus and colon cancers. These results indicate that tumor vascular endothelial cells express a common antigen in different tumor 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 antitumor effect in vivo. The immunoconjugate (TES-23-NCS) caused a marked regression of the tumor, KMT-17 in rats and Meth-A in mice. Thus, from a clinical view, TES-23 would be a novel drug carrier because of its high specificity to tumor vascular endothelium and its application to many types of cancer.
Insights
A novel monoclonal antibody (TES-23) targets tumor vascular endothelium, showing high specificity and accumulation in various cancers. This antibody, TES-23, demonstrates potential as an effective drug carrier for cancer therapy.
Area of Science:
- Oncology
- Immunology
- Biotechnology
Context:
- Targeted cancer therapies using monoclonal antibodies against tumor-associated antigens show limited clinical efficacy.
- Tumor physiology presents challenges for conventional anti-cancer treatments.
- Targeting tumor vascular endothelium offers a novel therapeutic strategy.
Purpose:
- To assess the tissue distribution of anti-tumor vascular endothelium monoclonal antibody (TES-23).
- To evaluate the potential of TES-23 as a drug carrier for cancer treatment.
Summary:
- Monoclonal antibody TES-23, developed against tumor-derived endothelial cells (TECs), demonstrated significant accumulation in various tumor models (KMT-17, Meth-A, Colon-26, HT-1080) after intravenous injection.
- Radioactivity of radiolabeled TES-23 was significantly higher in tumors compared to control antibodies, with minimal distribution to normal tissues.
- Immunostaining confirmed TES-23's specific binding to tumor endothelium across different species and cancer types, indicating a common tumor endothelial antigen.
- An immunoconjugate, TES-23-neocarzinostatin (TES-23-NCS), induced marked tumor regression in vivo, validating TES-23's efficacy as a drug delivery vehicle.
Impact:
- TES-23 exhibits high specificity for tumor vascular endothelium, suggesting its broad applicability across multiple cancer types.
- The findings support TES-23 as a promising novel drug carrier for enhanced cancer therapy.
- This approach addresses the limitations of current targeted therapies by exploiting tumor-specific vasculature.