In vivo therapy of hepatocellular carcinoma with a tumor-specific adenoviral vector expressing interleukin-2

Hum Gene Ther. 1997 Dec 10;8(18):2173-82. doi: 10.1089/hum.1997.8.18-2173.


A recombinant adenovirus (AdVAFP1-IL2) containing the murine alpha-fetoprotein (AFP) promoter was constructed to direct hepatocellular carcinoma (HCC)-specific expression of the human interleukin-2 (IL-2) gene. In vitro testing of AdVAFP1-IL2 showed HCC-specific IL-2 gene expression three to four orders of magnitude higher in AFP-producing HCC lines compared to non-AFP producing non-HCC lines. The in vivo efficacy and tumor specificity of AdVAFP1-IL2 was evaluated compared to AdVCMV-IL2 (in which the IL-2 gene is driven by the strong constitutive cytomegalovirus promoter) in the treatment of established human HCC (Hep 3B/Hep G2) xenografts growing in CB-17/SCID mice. Intratumoral injection of AdV resulted in growth retardation and regression in a majority of established hepatomas, but with a much wider therapeutic index and less systemic toxicity using the AFP vector. This study illustrates the superiority of using transcriptionally targeted recombinant AdV vectors in cytokine-based gene therapy.

Publication types

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

MeSH terms

  • Adenoviridae / genetics*
  • Animals
  • Carcinoma, Hepatocellular / therapy*
  • Cell Line, Transformed
  • Cloning, Molecular
  • Genetic Therapy / methods*
  • Genetic Vectors* / toxicity
  • HeLa Cells
  • Humans
  • Interleukin-2 / genetics*
  • Interleukin-2 / metabolism
  • Mice
  • Mice, SCID
  • Neoplasms, Experimental / therapy*
  • Promoter Regions, Genetic
  • Tumor Cells, Cultured
  • alpha-Fetoproteins / genetics


  • Interleukin-2
  • alpha-Fetoproteins