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Published on: January 29, 2019
Effective cancer targeting using an anti-tumor tissue vascular endothelium-specific monoclonal antibody (TES-23)
1Department of Biopharmaceutics, School of Pharmaceutical Sciences, Osaka University, Suita, Osaka 565-0871, Japan. mayumi@phs.osaka-u.ac.jp
Abstract:
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.
Insights
This study shows that an immunoconjugate using TES-23 antibody can target solid tumors by binding to tumor endothelial cells. This approach improved survival in mice with fibrosarcoma, suggesting potential for broader cancer treatment.
Area of Science:
- Oncology
- Immunology
- Biotechnology
Background:
- Immunoconjugate therapy for solid tumors faces challenges due to the physical barrier posed by tumor blood vessel endothelial cells.
- Previous work demonstrated that TES-23, an antibody targeting tumor endothelial cells, conjugated with neocarzinostatin (NCS), showed anti-tumor effects against KMT-17 fibrosarcoma.
Purpose of the Study:
- To investigate the efficacy of the TES-23-NCS immunoconjugate for targeting various solid tumors.
- To evaluate the anti-tumor effects and tumor accumulation of TES-23 in different tumor models.
Main Methods:
- Conjugation of TES-23 monoclonal antibody with neocarzinostatin (NCS).
- Administration of (125)I-labeled TES-23 to mice bearing Meth-A fibrosarcoma and Colon 26 adenocarcinoma.
- Assessment of tumor accumulation of TES-23 compared to control IgG.
- Evaluation of anti-tumor effects and survival rates in mice treated with the immunoconjugate.
Main Results:
- TES-23 demonstrated greater accumulation in Meth-A fibrosarcoma and Colon 26 adenocarcinoma tumors compared to control IgG.
- Treatment with the TES-23-NCS immunoconjugate resulted in improved survival rates in mice bearing Meth-A fibrosarcoma.
- No observable side effects were reported in the treated mice.
Conclusions:
- The TES-23 immunoconjugate shows promise for targeting tumor vasculature across different solid tumor types.
- The findings suggest the presence of common antigens on various tumor endothelial cells recognized by TES-23.
- This approach offers a potential strategy for effective cancer therapy with minimal toxicity.
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