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

Charles A. Leath, Manjula Kataram, Pradeep Bhagavatula, Rahul V. Gopalkrishnan, Paul Dent, Paul B. Fisher, Alexander Pereboev, Delicia Carey, Irina V. Lebedeva, Hidde J. Haisma, Ronald D. Alvarez, David T. Curiel, Parameshwar J. Mahasreshti

Research output: Contribution to journalArticlepeer-review

26 Scopus citations


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.

Original languageEnglish
Pages (from-to)352-362
Number of pages11
JournalGynecologic oncology
Issue number2
StatePublished - Aug 2004


  • Adenoviral vector
  • Ovarian carcinoma
  • Retargeting
  • mda-7/IL-24


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