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Analyzing Tumor and Tissue Distribution of Target Antigen Specific Therapeutic Antibody
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Analyzing Tumor and Tissue Distribution of Target Antigen Specific Therapeutic Antibody

Published on: May 16, 2020

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.

Biochemical and Biophysical Research Communications
|July 15, 1999
PubMed

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.

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