A novel tumor-specific replication-restricted adenoviral vector for gene therapy of hepatocellular carcinoma

Hum Gene Ther. 1999 Jul 1;10(10):1721-33. doi: 10.1089/10430349950017725.


Transducing and distributing a vector throughout a tumor mass are presently insufficient for effective cancer gene therapy. To overcome these difficulties an adenoviral vector was designed that would replicate specifically in tumor cells. This tumor-specific replication-restricted adenoviral (TSRRA) vector was constructed by requiring that the essential E1A gene be expressed from a tumor-specific promoter, namely, the alpha-fetoprotein (AFP) gene promoter. This promoter was chosen since the AFP gene is highly expressed in 70-80% of patients with hepatocellular carcinoma (HCC) but not in normal adults. HCC is one of the major worldwide causes of cancer death. A vector was constructed (AvE1a04i) and demonstrated to replicate in human AFP-producing HCC cell lines. However, little replication was observed in seven other, non-AFP-producing human cell lines, as well as primary cultures of normal human lung epithelial and endothelial cells. In addition, AvE1a04i was shown to prevent tumor growth of an ex vivo-transduced AFP-expressing HCC cell line but not a non-AFP-expressing cell line. Finally, in situ administration of AvE1a04i into preestablished tumors resulted in a greater than 50% long-term survival rate. This novel TSRRA vector for HCC demonstrated both specificity and efficacy in vitro and in vivo.

MeSH terms

  • Adenoviruses, Human* / genetics
  • Adenoviruses, Human* / physiology
  • Animals
  • Carcinoma, Hepatocellular / therapy*
  • Genetic Therapy / methods*
  • Genetic Vectors* / genetics
  • Genetic Vectors* / physiology
  • Humans
  • Liver Neoplasms / therapy*
  • Mice
  • Neoplasms, Experimental / therapy
  • Promoter Regions, Genetic*
  • Tumor Cells, Cultured
  • Virus Replication
  • alpha-Fetoproteins / genetics*


  • alpha-Fetoproteins