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肿瘤基因治疗中的 MDA-7/白细胞介素 24(IL-24):穿透/归巢肽的应用提高了疗效。

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

机构信息

a Department of Genetics and Molecular Biology, School of Medicine , Isfahan University of Medical Sciences , Isfahan , Iran.

b Department of Genetics and Molecular Biology, Pediatrics Inherited Diseases Research Center, Research Institute for Primordial Prevention of Non-Communicable Disease School of Medicine , Isfahan University of Medical Sciences , Isfahan , Iran.

出版信息

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.

摘要

简介

MDA-7/白细胞介素-24(IL-24)作为一种多效细胞因子,表现出特定的肿瘤抑制特性,引起了广泛关注。虽然其抗肿瘤诱导作用主要归因于内源性基因表达,但分泌型 MDA-7/IL-24 与同源受体的结合也通过不同途径触发癌细胞死亡。因此,精确地将分泌型 MDA-7/IL-24 靶向肿瘤细胞将使其更有效和更具特异性。

涵盖的领域

为了将可溶性细胞因子(特别是 MDA-7/IL-24)靶向肿瘤邻近部位,并提高其治疗效率,由于旁观者效应的改善,融合细胞穿透肽(CPPs)或肿瘤归巢肽(THPs)似乎是合理的。尽管内源性 mda-7/IL-24 的详细抗肿瘤机制已被广泛研究,但分泌型在这些活性中的意义以及 CPPs 或 THPs 对其的改善方法仍需要更多讨论。

专家意见

虽然 CPPs/THPs 的应用对于改善细胞因子基因治疗是可取的,但要创造 CPPs/THPs 与 MDA-7/IL-24 的融合,有些障碍是不可避免的。就我们的专业知识而言,本文讨论了 CPPs/THPs 的重要性、在融合结构中进行巧妙设计的必要性,以及它们在细胞因子基因治疗中的应用,特别关注 mda-7/IL-24。

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