Infectivity enhanced adenoviral-mediated mda-7/IL-24 gene therapy for ovarian carcinoma

Gynecol Oncol. 2004 Aug;94(2):352-62. doi: 10.1016/j.ygyno.2004.04.028.


Objective: Melanoma differentiation associated gene-7 [mda-7/Interleukin (IL)-24] has been identified as a novel anti-cancer agent, which specifically induces apoptosis in cancer cells but not in normal epithelial, endothelial and fibroblast cells. The objective of this study was to evaluate the anti-tumor effect of adenovirus-mediated mda-7/IL-24 (Ad.mda-7) gene therapy in ovarian carcinoma and further improve anti-tumor effect by enhancing infectivity of Ad.mda-7.

Methods: A panel of human ovarian carcinoma cells, OV-4, HEY, SKOV3, SKOV3.ip1 and control normal human mesothelial cells, were infected by a replication deficient recombinant adenovirus encoding mda-7/IL-24 and control virus Ad.CMV.Luc. After 72 h, apoptosis was evaluated by TUNEL and Hoechst staining and further quantified by fluorescent activated cell sorter (FACS) analysis. Infectivity of Ad.mda-7 was enhanced by retargeting it to CD40 or EGF receptors overexpressed on ovarian cancer cells. Subsequently, enhancement in apoptosis of CD40- or epidermal growth factor receptor (EGFR)-retargeted Ad.mda-7 was evaluated.

Results: Adenoviral-mediated delivery of mda-7 induces apoptosis ranging from 10-23% in human ovarian cancer cells tested with the highest percentage of apoptosis noted in SKOV3 cells. Minimal apoptosis was noted in normal mesothelial cells. CD40- or EGFR-retargeted Ad.mda-7 increased apoptosis by 10-32% when compared to that achieved with untargeted Ad.mda-7.

Conclusion: Ad.mda-7 exhibits ovarian cancer-specific apoptosis, but does not affect normal human mesothelial cells. Infectivity enhanced CD40- and EGFR-retargeted Ad.mda-7 augments apoptosis induction, thus increasing the therapeutic index and translational potential of Ad.mda-7 gene therapy.

Publication types

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

MeSH terms

  • Adenoviruses, Human / genetics
  • Adenoviruses, Human / pathogenicity
  • Adenoviruses, Human / physiology
  • Apoptosis / genetics
  • CD40 Antigens / metabolism
  • Cell Line, Tumor
  • Epithelial Cells / cytology
  • Epithelial Cells / physiology
  • Epithelial Cells / virology
  • ErbB Receptors / metabolism
  • Female
  • Genes, Tumor Suppressor
  • Genetic Therapy / methods*
  • Humans
  • Interleukins / genetics*
  • Interleukins / metabolism
  • Ovarian Neoplasms / genetics*
  • Ovarian Neoplasms / metabolism
  • Ovarian Neoplasms / therapy*
  • Ovarian Neoplasms / virology
  • Virus Replication


  • CD40 Antigens
  • Interleukins
  • interleukin-24
  • ErbB Receptors