Nature子刊:简约型纳米疫苗,助力癌症免疫治疗
2017/04/26
4月24日,Nature子刊《Nature Nanotechnology》在线发表一篇题为“A STING-activating nanovaccine for cancer immunotherapy”的文章,揭示了一种纳米疫苗PC7A NP,成功在多种患癌小鼠体内表现出抗肿瘤功效,有望助力癌症免疫治疗。


4月24日,Nature子刊《Nature Nanotechnology》在线发表一篇题为“A STING-activating nanovaccine for cancer immunotherapy”的文章,揭示了一种纳米疫苗PC7A NP,成功在多种患癌小鼠体内表现出抗肿瘤功效,有望助力癌症免疫治疗。

这一疫苗的亮点在于简约性——minimalist nanovaccine,由聚合纳米颗粒包裹肿瘤抗原而成。纳米疫苗能够刺激强烈的细胞毒性T细胞,具体而言,PC7A NP能够将肿瘤抗原实现高效的胞内传递,将抗原直接运输至引流淋巴结中的抗原呈递细胞。


激光会因为纳米疫苗溶液中的纳米颗粒而分散

文章通讯作者、德州大学西南医学中心的药理学和耳鼻喉科教授Jinming Gao带领团队完成了这一先创。这种简化版的疫苗能够精准的将肿瘤抗原呈递给免疫细胞,从而激活杀手T细胞,实现癌细胞的攻击。

它的实现依赖于干扰素基因刺激因子(stimulator of interferon genes,STING),这一配体蛋白被疫苗激活后,会进一步刺激机体启动免疫防御系统,最终对抗肿瘤。


研究团队构建了多种患癌小鼠模型,包括黑色素瘤、结直肠癌、HPV相关肿瘤。一系列动物试验表明,新型纳米疫苗能够减缓肿瘤的生长,并延长小鼠的生存期。

更可喜的是,当PC7A纳米疫苗与PD-1抗体结合使用时,研究人员发现它们表现出极大的协同效应,所有患癌小鼠都存活超60天,而且纳米疫苗能够让免疫系统产生对抗肿瘤的长期记忆。

研究人员认为,这一简化版纳米疫苗提供一种简单、安全、的抗肿瘤免疫治疗策略。未来,它可以与其他癌症治疗手段结合,进一步提高肿瘤治疗的效果,包括传统的放化疗以及其他肿瘤免疫治疗策略(免疫检查点抑制剂等)。

参考资料:

Nanoparticle vaccine shows potential as immunotherapy to fight multiple cancer types

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  • A STING-activating nanovaccine for cancer immunotherapy

    The generation of tumour-specific T cells is critically important for cancer immunotherapy1, 2. A major challenge in achieving a robust T-cell response is the spatiotemporal orchestration of antigen cross-presentation in antigen-presenting cells with innate stimulation. Here, we report a minimalist nanovaccine, comprising a simple physical mixture of an antigen and a synthetic polymeric nanoparticle, PC7A NP, which generates a strong cytotoxic T-cell response with low systemic cytokine expression. Mechanistically, the PC7A NP achieves efficient cytosolic delivery of tumour antigens to antigen-presenting cells in draining lymph nodes, leading to increased surface presentation while simultaneously activating type I interferon-stimulated genes. This effect is dependent on stimulator of interferon genes (STING), but not the Toll-like receptor or the mitochondrial antiviral-signalling protein (MAVS) pathway. The nanovaccine led to potent tumour growth inhibition in melanoma, colon cancer and human papilloma virus-E6/E7 tumour models. The combination of the PC7A nanovaccine and an anti-PD-1 antibody showed great synergy, with 100% survival over 60 days in a TC-1 tumour model. Rechallenging of these tumour-free animals with TC-1 cells led to complete inhibition of tumour growth, suggesting the generation of long-term antitumour memory. The STING-activating nanovaccine offers a simple, safe and robust strategy in boosting anti-tumour immunity for cancer immunotherapy.

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