Ligand-Mediated Targeting of Cytokine Interleukin-27 Enhances Its Bioactivity .

Fiche publication

Date publication

juin 2020

Journal

Molecular therapy. Methods & clinical development

Auteurs

Membres identifiés du Cancéropôle Est :
Dr CHAN-SENG Delphine

Tous les auteurs :
Figueiredo ML, Figueiredo Neto M, Salameh JW, Decker RE, Letteri R, Chan-Seng D, Emrick T

Lien Pubmed

https://www.ncbi.nlm.nih.gov/pubmed/32346551

Résumé

We have examined the role of a novel targeted cytokine, interleukin-27 (IL-27), modified at the C terminus with a dual targeting and therapeutic heptapeptide, in treating prostate cancer. IL-27 has shown promise in halting tumor growth and mediating tumor regression in several cancer models, including prostate cancer. We describe our findings on the effects of targeted IL-27 gene delivery on prostate cancer cells and and how the targeting enhances bioactivity of the IL-27 cytokine. We applied the IL-27 gene delivery protocol utilizing sonoporation (sonodelivery) with the goal of reducing prostate tumor growth in an immunocompetent TC2R C57/BL6 model. The reduction in tumor growth and effector cellular profiles implicate targeted IL-27 as more effective than an untargeted version of IL-27 in promoting bioactivity, as assessed by STAT1 and IFN-γ reporter genes. Moreover, enhanced antitumor effects and significantly higher accumulation of natural killer T (NKT) and CD8 effector cells in the tumors were observed. These results support a novel IL-27-based targeting strategy that is promising since it shows improved therapeutic efficacy while utilizing simple and effective sonodelivery methods.