Improvement of carcinoembryonic antigen-specific prodrug gene therapy for experimental colon cancer

Surgery. 2003 Mar;133(3):309-17. doi: 10.1067/msy.2003.73.


Background: Improvement of tumor-specific gene expression is very important for achieving successful effects in prodrug gene therapy for advanced cancer with metastatic lesions. We used the Cre/loxP system for enhancing carcinoembryonic antigen (CEA)-specific prodrug gene therapy of cytosine (CD)/5-fluorocytosine (5-FC) for the treatment of a colon cancer model accompanied with liver metastases.

Methods: Orthotopic colon cancer models were developed. Seven days later, adenovirus vector (3 x 10(9) pfu)was injected into the abdominal cavity, and 5-FC was administered for the next 10 days.

Results: In these models, the double administration of AxCEANCre expressing Cre recombinase under the control of the CEA promoter, and AxCALNLCD expressing the CD gene under the control of the CAG promoter by the Cre-mediated switching system, completely inhibited liver metastases, and significantly reduced primary tumor volume compared to the administration of Mock or AxCEACD (P <.001). The survival periods of the mice treated with AxCEANCre and AxCALNLCD were longer than mice treated with Mock or AxCEACD, and longer than the mice treated with AxCACD (P <.05).

Conclusions: The enhanced CEA-specific prodrug gene therapy using the Cre/loxP system was useful for the treatment of advanced colon cancer with liver metastases, implicating clinical application.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae
  • Antimetabolites, Antineoplastic / pharmacology*
  • Antimetabolites, Antineoplastic / therapeutic use
  • Carcinoembryonic Antigen / genetics
  • Carcinoembryonic Antigen / metabolism*
  • Colonic Neoplasms / drug therapy
  • Colonic Neoplasms / genetics
  • Colonic Neoplasms / immunology
  • Colonic Neoplasms / pathology
  • Colonic Neoplasms / therapy*
  • Cytosine / pharmacology*
  • Cytosine / therapeutic use
  • Cytosine Deaminase
  • Flucytosine / pharmacology
  • Gene Expression Regulation, Neoplastic / drug effects
  • Gene Transfer Techniques
  • Genetic Therapy / methods*
  • Genetic Vectors
  • HeLa Cells
  • Humans
  • Integrases / genetics*
  • Lac Operon
  • Liver Neoplasms / prevention & control*
  • Liver Neoplasms / secondary
  • Nucleoside Deaminases / genetics*
  • Prodrugs / pharmacology*
  • Prodrugs / therapeutic use
  • Promoter Regions, Genetic
  • Recombination, Genetic
  • Time Factors
  • Tumor Cells, Cultured
  • Viral Proteins / genetics*


  • Antimetabolites, Antineoplastic
  • Carcinoembryonic Antigen
  • Prodrugs
  • Viral Proteins
  • Cytosine
  • Flucytosine
  • Cre recombinase
  • Integrases
  • Nucleoside Deaminases
  • Cytosine Deaminase