Targeted sonodynamic therapy of cancer using a photosensitizer conjugated with antibody against carcinoembryonic antigen

Anticancer Res. 2002 May-Jun;22(3):1575-80.

Abstract

The goal of this study was to develop a strategy for the selective destruction of cancer cells by ultrasonic irradiation in the presence of an antibody-conjugated photosensitizer. To this end, a photoimmunoconjugate (PIC) was prepared between ATX-70, a photosensitizer of a gallium-porphyrin analogue, and F11-39, a high affinity monoclonal antibody (MAb) against carcinoembryonic antigen (CEA), which is often overexpressed in various carcinoma cells. This conjugate, designated F39/ATX-70, retained immunoreactivity against purified CEA and CEA-expressing cells as determined by enzyme-linked immunosorbent assay, flow cytometry and immunofluorescence microscopic analysis. The cytotoxicity of F39/ATX-70 against CEA-expressing human gastric carcinoma cells in vitro was found to be greater than that of ATX-70 when applied in combination with ultrasound irradiation. When in vivo anti-tumor effects in a mouse xenograft model were assessed, intravenous administration of F39/ATX-70 followed by ultrasonic irradiation produced a marked growth inhibition of tumor compared with irradiation alone or irradiation after administration of ATX-70. These results suggest that the PIC between anti-CEA MAb and ATX-70 may have applications in sonodynamic therapy where destruction of CEA-expressing tumor is required.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / immunology
  • Antibodies, Monoclonal / metabolism
  • Antibodies, Monoclonal / pharmacology
  • Antibodies, Monoclonal / toxicity
  • Antibody Specificity
  • Carcinoembryonic Antigen / immunology*
  • Carcinoembryonic Antigen / metabolism
  • Immunoconjugates / immunology
  • Immunoconjugates / metabolism
  • Immunoconjugates / pharmacology*
  • Immunoconjugates / toxicity
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Photosensitizing Agents / administration & dosage
  • Photosensitizing Agents / pharmacology*
  • Photosensitizing Agents / toxicity
  • Porphyrins / administration & dosage
  • Porphyrins / pharmacology*
  • Stomach Neoplasms / drug therapy
  • Stomach Neoplasms / immunology
  • Stomach Neoplasms / metabolism
  • Tumor Cells, Cultured
  • Ultrasonic Therapy / methods*
  • Xenograft Model Antitumor Assays

Substances

  • Antibodies, Monoclonal
  • Carcinoembryonic Antigen
  • Immunoconjugates
  • Photosensitizing Agents
  • Porphyrins
  • ATX 70