Ligand-Mediated Targeting of Cytokine Interleukin-27 Enhances Its Bioactivity In Vivo

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, includi...

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Veröffentlicht in:Molecular therapy. Methods & clinical development 2020-06, Vol.17, p.739-751
Hauptverfasser: Figueiredo, Marxa L., Figueiredo Neto, Manoel, Salameh, Janelle Wes, Decker, Richard E., Letteri, Rachel, Chan-Seng, Delphine, Emrick, Todd
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Sprache:eng
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Zusammenfassung: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 in vitro and in vivo 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.
ISSN:2329-0501
2329-0501
DOI:10.1016/j.omtm.2020.03.022