Issues in the development of gene therapy: preclinical experiments in E1A gene delivery

Oncol Rep. Mar-Apr 1999;6(2):257-62.


We recently completed a phase I trial of E1A gene therapy for patients with advanced breast or ovarian cancers. The trial's rationale was that E1A gene would downregulate HER-2/neu expression by repressing the gene's transcription, thus reversing the malignant phenotype. Our preclinical studies showed that i) transfection capabilities were not reduced in preparing E1A/cationic liposome complexes, ii) samples after ex vivo transfection, and iii) HER-2/neu gene expression could be quantified by quantitative imaging analysis. These results facilitated the translation of our basic research findings into a clinical trial and to obtain final approval from the National Institutes of Health Recombinant DNA Advisory Committee.

Publication types

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

MeSH terms

  • Adenovirus E1A Proteins / genetics*
  • Clinical Trials, Phase I as Topic
  • Down-Regulation
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Genes, Reporter
  • Genes, Viral*
  • Genetic Therapy / adverse effects
  • Genetic Therapy / methods*
  • Humans
  • Ovarian Neoplasms / therapy*
  • Receptor, ErbB-2 / genetics*
  • Recombinant Proteins / analysis
  • Recombinant Proteins / biosynthesis
  • Transcription, Genetic
  • Transfection
  • beta-Galactosidase / biosynthesis
  • beta-Galactosidase / genetics


  • Adenovirus E1A Proteins
  • Recombinant Proteins
  • Receptor, ErbB-2
  • beta-Galactosidase