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

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:

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

Article highlights

• In a supra-physiological level, MDA-7/IL-24, an unusual cytokine, exhibits different anti-tumor impacts.

• The increase in the bystander effect of MDA-7/IL-24, in turn, enhances its anti-tumor property.

• The CPPs/THPs are desirable to extend MDA-7/IL-24 and other cytokines gene therapy effects.

• Fusion of different CPPs/THPs with MDA-7/IL-24 could enhance its anti-tumor property by increasing the bystander effect and targeting.

• Tethering CPPs/THPs to cytokines should be designed in a way to prevent miss-folding and abnormal functions.

This box summarizes key points contained in the article.

Acknowledgments

The authors wish to thank Dr. N. Shokrpour at the Research Consultation Center (RCC) and Kowsar publishing group editing service for their insightful editorial services.

Declaration of interest

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Additional information

Funding

This work was supported by the Shiraz University of Medical sciences, under Grant Numbers [17292, 16162 and 10679] and Isfahan University of Medical Sciences.