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Pharmacokinetics and mechanism of action of a doxorubicin-monoclonal antibody 9.2.27 conjugate directed to a human-melanoma proteoglycan

Academic Article
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Overview

authors

  • Yang, H. M.
  • Reisfeld, Ralph

publication date

  • September 1988

journal

  • Journal of the National Cancer Institute  Journal

abstract

  • Doxorubicin (DXR) conjugated to a monoclonal antibody (MAb), 9.2.27, which recognizes a human melanoma-associated proteoglycan, effectively suppresses the growth of human melanoma xenografts and prolongs the life span of tumor-bearing athymic nude (nu/nu) mice. We have investigated further the mechanism(s) of this in vivo antitumor activity. Our results indicate that following iv injection, the DXR-MAb 9.2.27 conjugate is cleared from the circulation with typical biphasic kinetics, similar to the clearance process of the unconjugated MAb 9.2.27. In contrast, less than 10% of injected dose per milliliter of blood is found in the circulation at any given time after ip injection. Toxicity studies further indicate that DXR-MAb 9.2.27 conjugate is less toxic in vivo than the freely administered DXR, which is known to cause considerable cardiotoxic effects. Direct autoradiography demonstrates that the DXR-MAb 9.2.27 conjugate binds specifically to the tissue sections derived from a human melanoma xenograft of a nude mouse. A critical evaluation is given of the relevance of these findings and their impact on the design of future strategies for the immunochemotherapy of malignant melanoma.

subject areas

  • Animals
  • Antibodies, Monoclonal
  • Autoradiography
  • Doxorubicin
  • Electrophoresis, Polyacrylamide Gel
  • Female
  • Humans
  • Immunotoxins
  • Melanoma
  • Metabolic Clearance Rate
  • Mice
  • Mice, Inbred BALB C
  • Neoplasm Transplantation
  • Proteoglycans
  • Transplantation, Heterologous
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Identity

International Standard Serial Number (ISSN)

  • 0027-8874

Digital Object Identifier (DOI)

  • 10.1093/jnci/80.14.1154

PubMed ID

  • 3261803
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Additional Document Info

start page

  • 1154

end page

  • 1159

volume

  • 80

issue

  • 14

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