Salameh Janelle Wesleyn, Kumar Shreya, Rivera-Cruz Cosette Marie, Figueiredo Marxa Leao
The Department of Basic Medical Sciences, Purdue University, 625 Harrison St., West Lafayette, IN 47907, USA.
The Interdisciplinary Biomedical Sciences Program-The Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN 47907, USA.
Bioengineering (Basel). 2022 Feb 16;9(2):77. doi: 10.3390/bioengineering9020077.
An emerging approach in treating skeletal malignancies utilizes osteoimmunology to investigate new multifunctional immune-stimulatory agents that can simultaneously combat tumor growth and promote bone repair. We have hypothesized that cytokine Interleukin-27 (IL-27) is an excellent candidate biologic to help rebalance the prostate tumor cells and bone cell environment. In this work, we examined the proof of principle for a short, secreted luciferase (Nanoluc or Nluc) fusion with IL-27 to produce a novel cytokine-based biologic (Nluc-27), whereby we examined its efficacy in vitro in reducing prostate tumor growth and rebalancing bone cell proliferation and differentiation. This work demonstrates the targeting and anti-tumor efficacy of the Nluc-27 fusion cytokine in cancer and bone cell models. The fusion cytokine is detectable in conditioned media, and bioactive in different cell systems. This novel Nluc-27 cytokine will allow flexible incorporation of other targeting domains and may serve as flexible tool to augment IL-27's bioactivity and reengineer its efficacy against prostate tumor or bone cells, and may prove applicable to several other cell types for targeted gene therapy applications.
一种新兴的治疗骨骼恶性肿瘤的方法利用骨免疫学来研究新型多功能免疫刺激剂，这些药物能够同时对抗肿瘤生长并促进骨修复。我们推测细胞因子白细胞介素-27（IL-27）是一种优秀的候选生物制剂，有助于恢复前列腺肿瘤细胞与骨细胞环境之间的平衡。在这项研究中，我们验证了将短分泌型荧光素酶（纳米荧光素酶或Nluc）与IL-27融合以产生新型细胞因子生物制剂（Nluc-27）的原理，进而研究了其在体外降低前列腺肿瘤生长以及恢复骨细胞增殖和分化平衡方面的功效。这项研究证明了Nluc-27融合细胞因子在癌症和骨细胞模型中的靶向性和抗肿瘤功效。该融合细胞因子在条件培养基中可检测到，并且在不同细胞系统中具有生物活性。这种新型Nluc-27细胞因子将允许灵活整合其他靶向结构域，并且可能作为一种灵活的工具来增强IL-27的生物活性，重新设计其对前列腺肿瘤或骨细胞的疗效，并且可能证明适用于其他几种细胞类型的靶向基因治疗应用。
