E1B-55K-deleted adenovirus expressing E1A-13S by AFP-enhancer/promoter is capable of highly specific replication in AFP-producing hepatocellular carcinoma and eradication of established tumor

Mol Ther. 2002 May;5(5 Pt 1):627-34. doi: 10.1006/mthe.2002.0589.


Here, we constructed a recombinant replication-competent adenovirus (rRCAd; AdAFPep/Rep) that expresses both E1A-13S driven by the alpha-fetoprotein (AFP) enhancer/promoter (AFPep) lacking any silencers in the 5'-flanking region of the AFP gene, and 55K-deleted E1B driven by the cytomegalovirus (CMV) promoter. We then examined the feasibility of gene therapy utilizing this virus for AFP-producing hepatocellular carcinoma (HCC). AdAFPep/Rep lysed all the AFP-producing HCC cell lines (HuH7, HepG2, PLC/PRF/5 (P5)) examined at a multiplicity of infection (MOI) as low as 0.1 and did not lyse primary human hepatocytes (Hc) at a MOI as high as 100, indicating that the rRCAd virus can lyse AFP-producing HCC cells with a higher specificity and potency than previously reported. Furthermore, this virus was capable of complete eradication of a preestablished HuH7-cell tumor by a single intratumoral injection of 10(8) plaque-forming units (pfu) of AdAFPep/Rep. Thus, AdAFPep/Rep may be applicable for clinical use.

MeSH terms

  • Adenovirus E1A Proteins / genetics
  • Adenovirus E1A Proteins / metabolism*
  • Adenovirus E1B Proteins / genetics
  • Adenovirus E1B Proteins / metabolism*
  • Adenoviruses, Human / genetics
  • Adenoviruses, Human / physiology
  • Animals
  • Carcinoma, Hepatocellular / metabolism
  • Carcinoma, Hepatocellular / therapy*
  • Cell Survival / physiology
  • Colon / metabolism
  • Colon / pathology
  • Cytopathogenic Effect, Viral
  • DNA Primers / chemistry
  • Defective Viruses / genetics
  • Defective Viruses / physiology
  • Enhancer Elements, Genetic
  • Female
  • Genetic Therapy / methods*
  • Genetic Vectors / genetics
  • Genetic Vectors / physiology
  • Hepatocytes / metabolism
  • Hepatocytes / virology
  • Humans
  • Liver Neoplasms, Experimental / metabolism
  • Liver Neoplasms, Experimental / therapy*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Mutation
  • Plasmids
  • Polymerase Chain Reaction
  • Promoter Regions, Genetic
  • Tumor Cells, Cultured
  • Virus Replication
  • alpha-Fetoproteins / genetics*
  • alpha-Fetoproteins / metabolism*


  • Adenovirus E1A Proteins
  • Adenovirus E1B Proteins
  • DNA Primers
  • alpha-Fetoproteins