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首页> 外文期刊>Biomaterials >Development of an antigen-presenting cell-targeted DNA vaccine against melanoma by mannosylated liposomes
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Development of an antigen-presenting cell-targeted DNA vaccine against melanoma by mannosylated liposomes

机译：甘露糖基化脂质体开发针对黑色素瘤的抗原呈递细胞靶向DNA疫苗

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As part of our research involving the targeted delivery of plasmid DNA (pDNA) to antigen-presenting cells (APCs), we developed mannosylated cationic liposomes: N-[1-(2,3-dioleyloxy)propyl]-N,N,N-trimethylammonium chloride (DOTMA)/cholesten-5-yloxy-N-(4-((1-imino-2-d-thiomannosyl-ethyl)amino)butyl)formamide (Man-C4-Chol)/Chol (Man liposomes). In this study, we used melanoma-associated antigen expressing pDNA; pUb-M and Man liposomes to create a novel APC-targeted DNA vaccine against melanoma and examined its potency by measuring the Ub-M mRNA expression in splenic dendritic cells and macrophages, the cytotoxic T lymphocyte (CTL) activity against melanoma B16BL6 cells and the melanoma B16BL6-specific anti-tumor effect after intraperitoneal (i.p.) administration. We verified that Man lipoplex induces significantly higher pUb-M gene transfection into dendritic cells and macrophages than unmodified lipoplex and naked DNA and it also strongly induces CTL activity against melanoma, inhibits its growth and prolongs the survival after tumor challenge compared with unmodified liposomes and the standard method (naked pDNA, intramuscular (i.m.)). These results demonstrate that Man liposomes are a potent APCs-targeted vector that induce strong immunopotency of DNA vaccine against melanoma.
机译：作为涉及将质粒DNA（pDNA）靶向递送至抗原呈递细胞（APC）的研究的一部分，我们开发了甘露糖基化阳离子脂质体：N- [1-（2,3-二醇基氧基）丙基] -N，N，N -三甲基氯化铵（DOTMA）/胆甾烯基-5-基氧基-N-（4-（（1-亚氨基-2-d-硫代甘露糖基-乙基）氨基）丁基）甲酰胺（Man-C4-Chol）/ Chol（Man脂质体） 。在这项研究中，我们使用了黑色素瘤相关抗原表达的pDNA。 pUb-M和Man脂质体可产生针对APC的新型黑色素瘤DNA疫苗，并通过测量脾脏树突状细胞和巨噬细胞中Ub-M mRNA的表达，针对黑色素瘤B16BL6细胞的细胞毒性T淋巴细胞（CTL）活性以及腹膜内（ip）给药后黑色素瘤B16BL6特异性抗肿瘤作用。我们证实，与未修饰的脂质体和未修饰的脂质体相比，Man lipoplex诱导的pUb-M基因转染进入树突状细胞和巨噬细胞的比例明显高于未修饰的脂质体和裸露的DNA，并且还强烈诱导了针对黑素瘤的CTL活性，抑制了其生长并延长了肿瘤攻击后的存活时间。标准方法（裸露的pDNA，肌内（im））。这些结果证明，人脂质体是靶向APC的有效载体，其诱导针对黑素瘤的DNA疫苗的强免疫力。

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