新功能、新界面、新体验,扫描即可下载生物谷APP!
首页 » 癌症研究 » Nanoscale:新型纳米疫苗可增强癌症免疫疗法的效应 降低副作用

Nanoscale:新型纳米疫苗可增强癌症免疫疗法的效应 降低副作用

来源:生物谷 2016-08-31 22:39

图片来源:www.sciencedaily.com

2016年8月31日 讯 /生物谷BIOON/ --最近,一项刊登于国际杂志Nanoscale上的研究报告中,来自美国国家生物医学成像和生物工程研究所的研究人员通过研究开发出了一种新型纳米疫苗,其可以帮助开发出治疗癌症免疫疗法的新方法而且降低疗法的副作用;这种纳米疫苗可以有效运输特殊的DNA序列至免疫细胞中,这种来源于细菌DNA中的序列可以被用来诱发机体的免疫反应,同时该疫苗还可以保护机体中的DNA免于被破坏。

肿瘤可以通过抑制免疫系统识别并杀灭癌细胞的能力来逃脱免疫系统的攻击,而免疫疗法的目的就是调节机体的免疫系统以便其可以更加有效地对肿瘤发起攻击。免疫疗法的其中一种方法就是将未甲基化的胞嘧啶-鸟嘌呤寡聚脱氧核苷酸(CpG)的外源序列引入到机体中,CpGs是一种存在于细菌中但在哺乳动物机体中非常罕见的不同于DNA序列的模式,当其被注射到人类机体中时,CpGs可以扮演一种危险的信号来诱发免疫反应;近日多项临床试验都将CpGs直接注射到肿瘤中来作为一种方法,去激活附近的免疫细胞使得免疫细胞可以攻击肿瘤组织。

尽管具有一定的潜力,但基于CpG的免疫疗法却面临着一定的挑战,本文中,研究者通过研究开发了一种“DNA无机杂交纳米疫苗”(hNVs);为了确定hNVs疫苗在小鼠免疫细胞中的行为,研究者将荧光分子掺入到免疫细胞中以便可以观察其行为,他们发现,hNVs可以直接被两种不同类型的免疫细胞所摄入,同时其还会诱导免疫细胞激活。随后研究者对黑色素瘤小鼠进行研究,他们将hNVs或CpG分子注射到小鼠机体中,相比CpG分子而言,hNVs在肿瘤环境中停留的时间较长,当间隔6天分别注射后,hNVs就可以对小鼠机体的肿瘤有着明显的抑制作用,在疗法37天后接受hNVs疫苗的小鼠中有五分之二都存活了下来,而接受CpG的小鼠没有一只存活下来。

此外,除了CpGs诱导的免疫反应外,hNVs还会通过降低从肿瘤中渗入到血液中CpG的水平,来减少和CpG注射相关的副作用;研究者指出,hNVs的另外一个优势就是其可以稳定CpGs以便在储存和运输过程中CpGs并不需要冷藏。

下一步研究人员计划调查hNVs结合肿瘤特异性抗原的效应,通过加入这些特异性的蛋白抗原分子,研究者希望可以更进一步指导免疫细胞发挥作用,促进癌变细胞被杀灭;当然研究者也非常感兴趣将hNVs同化疗或者放疗方法相结合来治疗癌症。(生物谷Bioon.com)

本文系生物谷原创编译整理,欢迎转发,转载需授权!点击  获取授权 。更多资讯请下载 生物谷app.

DNA–inorganic hybrid nanovaccine for cancer immunotherapy

Guizhi Zhu,a Yijing Liu,a Xiangyu Yang,a Young-Hwa Kim,a Huimin Zhang,a Rui Jia,b Hsien-Shun Liao,c Albert Jin,c Jing Lin,c Maria Aronova,c Richard Leapman,c Zhihong Nie,d Gang Niua and Xiaoyuan Chen*a

Cancer evolves to evade or compromise the surveillance of the immune system, and cancer immunotherapy aims to harness the immune system in order to inhibit cancer development. Unmethylated CpG dinucleotide-containing oligonucleotides (CpG), a class of potent adjuvants that activate the toll-like receptor 9 (TLR9) located in the endolysosome of many antigen-presenting cells (APCs), are promising for cancer immunotherapy. However, clinical application of synthetic CpG confronts many challenges such as suboptimal delivery into APCs, unfavorable pharmacokinetics caused by limited biostability and short in vivo half-life, and side effects associated with leaking of CpG into the systemic circulation. Here we present DNA–inorganic hybrid nanovaccines (hNVs) for efficient uptake into APCs, prolonged tumor retention, and potent immunostimulation and cancer immunotherapy. hNVs were self-assembled from concatemer CpG analogs and magnesium pyrophosphate (Mg2PPi). Mg2PPi renders hNVs resistant to nuclease degradation and thermal denaturation, both of which are demanding characteristics for effective vaccination and the storage and transportation of vaccines. Fluorophore-labeled hNVs were tracked to be efficiently internalized into the endolysosomes of APCs, where Mg2PPi was dissolved in an acidic environment and thus CpG analogs were exposed to hNVs. Internalized hNVs in APCs led to (1) elevated secretion of proinflammatory factors, and (2) elevated expression of co-stimulatory factors. Compared with molecular CpG, hNVs dramatically prolonged the tissue retention of CpG analogs and reduced splenomegaly, a common side effect of CpG. In a melanoma mouse model, two injections of hNVs significantly inhibited the tumor growth and outperformed the molecular CpG. These results suggest hNVs are promising for cancer immunotherapy.

相关会议推荐

2016纳米技术与医学前沿研讨会

会议时间:2016.11.18-2016.11.19     会议地点:苏州

会议详情: http://www.bioon.com/z/2016nm/

温馨提示:87%用户都在生物谷APP上阅读,扫描立刻下载! 天天精彩!


相关标签

最新会议 培训班 期刊库