RNA cancer vaccines: developing mRNA nanovaccine with self-adjuvant property for cancer immunotherapy.
RNA cancer vaccines: developing mRNA nanovaccine with self-adjuvant property for cancer immunotherapy.
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RNA癌症疫苗：开发具有自我辅助特性的mRNA纳米疫苗，用于癌症免疫治疗。
DOI：
10.1080/21645515.2021.1921524
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发表时间：
2021
期刊：
影响因子：
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通讯作者：
Xia Xiaojun
中科院分区：
文献类型：
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作者：
Zhang Hongxia;Xia Xiaojun
基于信使核糖核酸(Messenger RNA，mRNA)的肿瘤疫苗已成为发展个性化和有效的抗肿瘤免疫治疗的一种流行方法。为了达到强大的抗肿瘤效果，编码肿瘤抗原的mRNA需要在树突状细胞中高效地递送和翻译，以实现高效的抗原提呈；同时，疫苗将通过刺激先天免疫反应来发挥佐剂作用，以促进获得性免疫的充分激活。最近，我们报道了一种最低限度的纳米疫苗，它用一种名为C1的类脂材料制备了编码肿瘤抗原的mRNA，它可以有效地将mRNA输送到树突状细胞中，同时刺激Toll样受体4(TLR4)，共同诱导T细胞激活。重要的是，C1mRNA纳米疫苗在几种肿瘤小鼠模型上显示出显著的抗肿瘤效果。在这里，我们讨论了树突状细胞中纳米载体促进的mRNA传递和翻译，纳米载体的自佐剂特性，个性化肿瘤抗原选择的挑战，以及针对免疫抑制的肿瘤微环境开发有效的mRNA癌症疫苗的潜在策略。
Messenger RNA (mRNA)-based cancer vaccine has become a popular approach for developing personalized and effective antitumor immunotherapy. To achieve robust antitumor efficacy, mRNA-encoding tumor antigens needs to be efficiently delivered and translated in dendritic cells for efficient antigen presentation; meanwhile, the vaccine would have adjuvant effect by stimulating innate immune response to boost the full activation of adaptive immunity. Recently, we reported a minimalist nanovaccine by formulating tumor antigen-encoding mRNA with a lipid-like material named C1, which could efficiently deliver mRNA into dendritic cells with simultaneous Toll-like receptor 4 (TLR4) stimulation, together induced T cell activation. Importantly, C1 mRNA nanovaccine exhibited significant antitumor efficacy on several tumor mouse models. Here, we discuss the nanovector-facilitated mRNA delivery and translation in dendritic cells, the self-adjuvant property of nanovectors, the challenges of personalized tumor antigen selection, and the potential strategies for developing efficacious mRNA cancer vaccines targeting the immunosuppressive tumor microenvironment.