Melanoma differentiation associated gene-7 (mda-7)/IL-24: A 'magic bullet' for cancer therapy?

Devanand Sarkar, Irina V. Lebedeva, Pankaj Gupta, Luni Emdad, Moira Sauane, Paul Dent, David T. Curiel, Paul B. Fisher

Research output: Contribution to journalReview article

55 Scopus citations

Abstract

An ideal cancer gene therapy would selectively kill cancer cells without harming normal cells and induce multipronged 'bystander' antitumor effects, facilitating eradication of both primary and metastatic tumors. Melanoma differentiation associated gene-7 (mda-7)/interleukin-24 (IL-24) exhibits all of these attributes and more. It induces cancer-selective apoptosis, inhibits angiogenesis, stimulates an antitumor immune response, sensitizes cancer cells to radiation and other modalities of conventional therapies, and exhibits profound 'bystander' activity eliminating both primary and distant tumors in animal models. Moreover, a replication-incompetent adenovirus expressing mda-7/IL-24, Ad.mda-7 (INGN-241), has now undergone evaluation in a Phase I clinical trial for multiple solid tumors, including melanomas, and has demonstrated safety and significant objective clinical activity. Considering these exciting observations, mda-7/IL-24 is being hailed as a 'magic bullet' for cancer gene therapy. This review elaborates on the pleiotropic properties of mda-7/IL-24 and unravels novel aspects of the molecule mandating future studies and expanded clinical applications.

Original languageEnglish
Pages (from-to)577-586
Number of pages10
JournalExpert opinion on biological therapy
Volume7
Issue number5
DOIs
StatePublished - May 1 2007
Externally publishedYes

Keywords

  • Antiangiogenesis
  • Antitumor agents
  • Bipartite adenovirus
  • Bystander antitumor activity
  • Cancer-selective apoptosis
  • Conditional replication-competent adenovirus
  • ER stress
  • IL-10 family member
  • Immune modulation
  • Radiosensitization
  • Reactive oxygen species

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