MDA-7/interleukin 24 (IL-24) in tumor gene therapy: application of tumor penetrating/homing peptides for improvement of the effects

Expert Opin Biol Ther. 2019 Mar;19(3):211-223. doi: 10.1080/14712598.2019.1566453. Epub 2019 Jan 21.

Abstract

Introduction: MDA-7/Interleukin-24 (IL-24), as a pleiotropic cytokine, exhibits a specific tumor suppression property that has attracted a great deal of attention. While its anti-tumor induction is mostly attributed to endogenous gene expression, attachment of secreted MDA-7/IL-24 to cognate receptors also triggers the death of cancerous cell via different pathways. Therefore, precise targeting of secreted MDA-7/IL-24 to tumor cells would render it more efficacy and specificity.

Areas covered: In order to target soluble cytokines, particularly MDA-7/IL-24 to the neighbor tumor sites and enhance their therapeutic efficiency, fusing with cell penetrating peptides (CPPs) or Tumor homing peptides (THPs) seems logical due to the improvement of their bystander effects. Although the detailed anti-tumor mechanisms of endogenous mda-7/IL-24 have been largely investigated, the significance of the secreted form in these activities and methods of its improving by CPPs or THPs need more discussion.

Expert opinion: While the employment of CPPs/THPs for the improvement of cytokine gene therapy is desirable, to create fusions of CPPs/THPs with MDA-7/IL-24, some hurdles are not avoidable. Regarding our expertise, herein, the importance of CPPs/THPs, needs for their elegant designing in a fusion structure, and their applications in cytokine gene therapy are discussed with a special focus on mda-7/IL-24.

Keywords: IL-24 cytokine; Tumor gene therapy; cell penetrating peptides (CPPs); melanoma differentiation-associated gene-7 (MDA-7); tumor homing peptides (THPs).

Publication types

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

MeSH terms

  • Adjuvants, Immunologic / therapeutic use*
  • Apoptosis / drug effects
  • Bystander Effect
  • Drug Synergism
  • Genes, Neoplasm
  • Genetic Therapy*
  • Humans
  • Interleukins / therapeutic use*
  • Neoplasms / therapy*

Substances

  • Adjuvants, Immunologic
  • Interleukins
  • interleukin-24