Powerful anti-colon cancer effect of modified nanoparticle-mediated IL-15 immunogene therapy through activation of the host immune system.

Powerful anti-colon cancer effect of modified nanoparticle-mediated IL-15 immunogene therapy through activation of the host immune system.
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改良纳米颗粒介导的 IL-15 免疫基因疗法通过激活宿主免疫系统产生强大的抗结肠癌作用

DOI:
10.7150/thno.24157
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发表时间:
2018
期刊:
影响因子:
12.4
通讯作者:
Wei Y
Wei Y
中科院分区:
医学1区
文献类型:
--
作者:
Liu X;Li Y;Sun X;Muftuoglu Y;Wang B;Yu T;Hu Y;Ma L;Xiang M;Guo G;You C;Gao X;Wei Y

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基本原理:结直肠癌(CRC)是世界上第三大最常见的诊断癌症。在过去的几年里,免疫疗法在CRC治疗中表现出相当大的临床益处,并且用于癌症治疗的免疫疗法的数量每年都在继续攀升。白细胞介素-15(IL-15)是一种有效的促炎细胞因子,已成为治疗CRC的候选免疫调节剂。研究方法:本研究采用DOTAP和MPEG-PLA(DMA)自组装的方法开发了一种新型基因递送系统,将pIL 15携带在该系统中,命名为DMA-pIL 15,并用于治疗荷瘤小鼠。结果如下:体外实验表明,转染DMA-pIL 15的CT 26细胞培养上清可抑制CT 26细胞的生长并诱导细胞凋亡。用DMA-pIL 15复合物治疗荷瘤小鼠通过抑制血管生成、促进细胞凋亡和通过激活宿主免疫系统减少增殖而显著抑制体内皮下和腹膜模型中的肿瘤生长。结论:IL-15质粒与DMA复合物有望成为临床治疗大肠癌的实验性新药。
Rationale: Colorectal cancer (CRC) is the third most commonly diagnosed cancer around the world. Over the past several years, immunotherapy has demonstrated considerable clinical benefit in CRC therapy, and the number of immunologic therapies for cancer treatment continues to climb each year. Interleukin-15 (IL15), a potent pro-inflammatory cytokine, has emerged as a candidate immunomodulator for the treatment of CRC. Methods: In this study, we developed a novel gene delivery system with a self-assembly method using DOTAP and MPEG-PLA (DMA) to carry pIL15, denoted as DMA-pIL15 which was used to treat tumor-bearing mice. Results: Supernatant from lymphocytes treated with supernatant derived from CT26 cells transfected with DMA-pIL15 inhibited the growth of CT26 cells and induced cell apoptosis in vitro. Treatment of tumor-bearing mice with DMA-pIL15 complex significantly inhibited tumor growth in both subcutaneous and peritoneal models in vivo by inhibiting angiogenesis, promoting apoptosis, and reducing proliferation through activation of the host immune system. Conclusion: The IL-15 plasmid and DMA complex showed promise for treating CRC clinically as an experimental new drug.
DOI: 10.18632/oncotarget.10264
发表时间: 2016-08-02
期刊: Oncotarget
影响因子: --
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Di Scala M;Gil-Fariña I;Olagüe C;Vales A;Sobrevals L;Fortes P;Corbacho D;González-Aseguinolaza G
通讯作者: González-Aseguinolaza G
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发表时间: 2012-04-15
期刊: Cancer research
影响因子: 11.2
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DOI: 10.1126/science.8178155
发表时间: 1994-05-13
期刊: SCIENCE
影响因子: 56.9
作者:
GRABSTEIN, KH;EISENMAN, J;GIRI, JG
通讯作者: GIRI, JG
DOI: 10.1038/nature14418
发表时间: 2015-04-30
期刊: NATURE
影响因子: 64.8
作者:
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通讯作者: Lu, Xiongbin
DOI: 10.1016/s1525-0016(03)00222-3
发表时间: 2003-10-01
期刊: MOLECULAR THERAPY
影响因子: 12.4
作者:
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通讯作者: Mazda, O