Targeting strategy for gene delivery to carcinoembryonic antigen-producing cancer cells by retrovirus displaying a single-chain variable fragment antibody

Hum Gene Ther. 1998 Jan 20;9(2):235-48. doi: 10.1089/hum.1998.9.2-235.

Abstract

Cancer-specific antigens are promising targets for the specific delivery of certain drugs or genes to cancer cells in cancer therapy. Carcinoembryonic antigen (CEA) is one of the cancer-associated antigens predominantly detected in the gastrointestinal cancer of the colon and stomach. Targeting strategies for CEA-producing cancer cells have been thoroughly developed mainly by the production of monoclonal antibodies to CEA and further single-chain variable fragment (scFv) antibodies. Here, we have generated Moloney murine leukemia virus-derived retroviral vectors co-displaying an anti-CEA scFv-envelope chimeric protein and an unmodified envelope protein to deliver a gene for herpes simplex virus thymidine kinase (HSV-tk) or Escherichia coli beta-galactosidase. The harvested viruses successfully incorporated the chimeric envelope protein as well as the unmodified envelope into the viral particles, and specifically bound to and infected human CEA-producing cancer cells via recognition of CEA, depending on the CEA-producing phenotype of the target cells. These results may have significant implications for the use of scFv directed against tumor-specific antigens for targeting specific antigen-producing cancer cells, a potential step toward in vivo cancer therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells
  • Animals
  • Carcinoembryonic Antigen / biosynthesis*
  • Carcinoembryonic Antigen / genetics*
  • Gastrointestinal Neoplasms / genetics
  • Gastrointestinal Neoplasms / metabolism
  • Gastrointestinal Neoplasms / virology*
  • Gene Targeting*
  • Gene Transfer Techniques*
  • Genetic Vectors / chemical synthesis
  • HeLa Cells
  • Humans
  • Immunoglobulin Fragments / genetics*
  • Immunoglobulin Variable Region / genetics*
  • Leukemia Virus, Murine / genetics
  • Leukemia Virus, Murine / metabolism
  • Mice
  • Phenotype
  • Tumor Cells, Cultured
  • Viral Envelope Proteins / genetics
  • Virus Assembly / genetics

Substances

  • Carcinoembryonic Antigen
  • Immunoglobulin Fragments
  • Immunoglobulin Variable Region
  • Viral Envelope Proteins