Messenger RNA vaccine based on recombinant MS2 virus-like particles against prostate cancer
Messenger RNA vaccine based on recombinant MS2 virus-like particles against prostate cancer
复制标题
基于重组 MS2 病毒样颗粒的抗前列腺癌信使 RNA 疫苗
DOI：
10.1002/ijc.28482
复制
发表时间：
2014-04-01
影响因子：
6.4
通讯作者：
Wang, Lunan
中科院分区：
文献类型：
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作者：
Li, Jinming;Sun, Yanli;Wang, Lunan
前列腺癌（PCa）是西方男性人群中最常见的癌症，死亡率高。最近，基于免疫疗法的替代方法，包括针对PCa的mRNA疫苗，已经显示出治疗前景。然而，mRNA疫苗存在mRNA不稳定、金颗粒成本高、转染树突状细胞的体外生产规模有限等缺点，限制了其发展。本文中，重组噬菌体MS 2病毒样颗粒（VLP）基于19个核苷酸的RNA适体与噬菌体MS 2外壳蛋白的相互作用，成功地解决了这些问题，其中靶mRNA被MS 2衣壳包装。MS 2 VLPmRNA疫苗可通过重组蛋白技术制备，无毒，耐RNase。我们发现，包装的mRNA被翻译成蛋白质，早在12小时后被巨噬细胞吞噬。此外，MS 2 VLPmRNA疫苗诱导了较强的体液和细胞免疫应答，尤其是抗原特异性细胞毒性T淋巴细胞（CTL）和平衡的Th 1/Th 2应答，而不上调CD 4（+）调节性T细胞，并完全保护C57 BL/6小鼠免受PCa的侵害。作为治疗性疫苗，基于MS 2 VLP的mRNA疫苗延迟肿瘤生长。我们的研究结果为基于MS 2 VLP的mRNA疫苗的有效性和安全性提供了概念证明，为mRNA疫苗提供了一种新的递送途径，对PCa的预防和治疗具有重要的临床价值。基于mRNA疫苗接种的免疫疗法是一种很有前途的对抗前列腺癌的方法，但mRNA的不稳定性和其他因素可能会限制其效用。然而，根据这项研究，其中一些因素可以通过基于噬菌体MS 2病毒样颗粒（VLP）的mRNA疫苗来克服。使用重组蛋白技术制备基于MS 2 VLP的疫苗，当在小鼠模型中进行测试时，发现其无毒并刺激体液和细胞免疫应答，完全保护小鼠免受前列腺癌的侵害。
Prostate cancer (PCa) is the most diagnosed cancer in the western male population with high mortality. Recently, alternative approaches based on immunotherapy including mRNA vaccines for PCa have shown therapeutic promise. However, for mRNA vaccine, several disadvantages such as the instability of mRNA, the high cost of gold particles, the limited production scale for mRNA-transfected dendritic cells in vitro, limit their development. Herein, recombinant bacteriophage MS2 virus-like particles (VLPs), which based on the interaction of a 19-nucleotide RNA aptamer and the coat protein of bacteriophage MS2, successfully addressed these questions, in which target mRNA was packaged by MS2 capsid. MS2 VLP-based mRNA vaccines were easily prepared by recombinant protein technology, nontoxic and RNase-resistant. We show the packaged mRNA was translated into protein as early as 12 hr after phagocytosed by macrophages. Moreover, MS2 VLP-based mRNA vaccines induced strong humoral and cellular immune responses, especially antigen-specific cytotoxic T-lymphocyte (CTL) and balanced Th1/Th2 responses without upregulation of CD4(+) regulatory T cells, and protected C57BL/6 mice against PCa completely. As a therapeutic vaccine, MS2 VLP-based mRNA vaccines delayed tumor growth. Our results provide proof of concept on the efficacy and safety of MS2 VLP-based mRNA vaccine, which provides a new delivery approach for mRNA vaccine and implies important clinical value for the prevention and therapy of PCa.What's new? Immunotherapy based on mRNA vaccination is a promising means of fighting prostate cancer, but mRNA instability and other factors could limit its utility. Some of those factors, however, may be overcome with an mRNA vaccine based on bacteriophage MS2 virus-like particles (VLPs), according to this study. MS2 VLP-based vaccines were prepared using recombinant protein technology, and when tested in a mouse model were found to be nontoxic and to stimulate humoral and cellular immune responses, fully protecting mice against prostate cancer.