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.

中文翻译：

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配体介导的细胞因子白介素27靶向增强其体内生物活性。

我们已经检查了新型靶向细胞因子白介素27（IL-27），在C末端用双重靶向和治疗性七肽修饰，在治疗前列腺癌中的作用。IL-27在阻止包括前列腺癌在内的几种癌症模型中的肿瘤生长和介导肿瘤消退方面显示出了希望。我们描述了在体外和体内靶向IL-27基因递送对前列腺癌细胞的影响以及靶向如何增强IL-27细胞因子生物活性的发现。我们应用了利用声纳穿孔（sonodelivery）的IL-27基因递送方案，目的是在具有免疫功能的TC2R C57 / BL6模型中减少前列腺肿瘤的生长。肿瘤生长和效应细胞特征的降低暗示靶向IL-27在促进生物活性方面比非靶向IL-27更有效，由STAT1和IFN-γ报告基因评估。此外，观察到增强的抗肿瘤作用以及肿瘤中天然杀伤性T（NKT）和CD8效应细胞的显着增加。这些结果支持了一种新颖的基于IL-27的靶向策略，该策略是有前途的，因为它在利用简单而有效的超声递送方法的同时显示了更高的治疗功效。