Targeting and eradicating cancer cells by a prostate-specific vector carrying the diphtheria toxin A gene

Cancer Gene Ther. 2000 Jul;7(7):991-6. doi: 10.1038/sj.cgt.7700197.


Prostate cancer is the most commonly diagnosed malignancy in American men. Developing gene therapy for prostate cancer is important, because there is no effective treatment for patients in the advanced stages of this disease. A tissue-specific promoter to transcriptionally target cancer cells is a promising approach for gene therapy of prostate cancer. We previously constructed a prostate tissue-specific promoter based on the proximal promoter and the upstream regulatory sequence of the prostate-specific antigen gene. In the experiments described here, we modified our prostate-specific promoter to drive the A domain of the diphtheria toxin gene (DTA) in a plasmid vector. The plasmid vector can be efficiently transfected into cell lines, using a liposome-mediated transfection method. In the transfected prostate cell line, LNCaP, the DTA gene was actively transcribed, and significant inhibition of protein synthesis and cytopathic effects was observed. However, no pathogenic effects were apparent in the control cell lines. The highly specific and efficient cytopathicity of the DTA gene vector is therefore potentially useful for systemic treatment of patients with metastatic prostate cancer.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Dihydrotestosterone / pharmacology
  • Diphtheria Toxin / therapeutic use*
  • Genetic Therapy*
  • Genetic Vectors*
  • Humans
  • Immunotoxins
  • Liposomes
  • Luminescent Proteins / genetics
  • Luminescent Proteins / metabolism
  • Male
  • Peptide Fragments / therapeutic use*
  • Plasmids
  • Promoter Regions, Genetic
  • Prostate-Specific Antigen / genetics*
  • Prostate-Specific Antigen / metabolism
  • Prostatic Neoplasms / metabolism
  • Prostatic Neoplasms / therapy*
  • Transfection
  • Tumor Cells, Cultured


  • Diphtheria Toxin
  • Immunotoxins
  • Liposomes
  • Luminescent Proteins
  • Peptide Fragments
  • diphtheria toxin fragment A
  • Dihydrotestosterone
  • Prostate-Specific Antigen