研究者Haifa Shen博士表示,仅需要向动物模型注射一个剂量的癌症疫苗或许就可以完全抑制肿瘤的生长,而本文的研究结果完全出乎我们的想象;利用多孔硅微粒(PSMs)进行体内和体外实验,结果显示,微粒可以在肿瘤活性和生长局部位点刺激产生强烈长效的先天性免疫反应。研究者首次表明,硅微粒可以作为一种载体对肿瘤抗原进行持续释放并且进行加工处理,但最重要的是研究者发现硅微粒本身就足以刺激机体1型干扰素效应,而且可以通过一种抗原呈递细胞转移至另外一种从而来维持长期的抗原释放效应。
在过去一年大约有23.5万女性被诊断为乳腺癌,而且每年有超过4万个体死于该疾病,开发一种抵御HER2的癌症疫苗或可帮助训练机体免疫系统来识别过表达HER2的癌细胞,从而将其摧毁,同时也不会对健康细胞带来任何副作用,但截至目前开发抵御HER2的癌症疫苗只取得了一些初步进展。
研究者指出,靶向作用HER2癌症蛋白质的疫苗目前正在开发中,但这些疫苗因为低效率地运输大多不是很有效果,而本文中研究者开发的由PSM介导的癌症疫苗不仅具有足够的潜力来靶向杀灭肿瘤细胞,而且可以修饰肿瘤的微环境使其可以癌细胞可以很轻松地被杀灭。PSM重要的一方面就是其可以刺激机体自身的免疫系统来攻击癌症,PSMs可以持续性地刺激呈递抗原细胞使其激活T细胞,同时其还会修饰肿瘤微环境以便毒性T细胞可以维持其活性。
PSMs的应用可以作为多种癌症疫苗的开发,而且可以装载多种诊断单一疫苗靶点的抗原来增强疫苗的效力;最后研究者Shen说道,本文研究中除了开发一种高效的乳腺癌疫苗外,我们也阐明了PSMs的多功能性,我们希望其可以作为一种平台来帮助更多的科学家们开发多种类型癌症的疫苗,从而为改善癌症患者的生存质量带来巨大帮助。
doi:10.1016/j.celrep.2015.04.009
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Porous Silicon Microparticle Potentiates Anti-Tumor Immunity by Enhancing Cross-Presentation and Inducing Type I Interferon Response
Xiaojun Xia, Junhua Mai, Rong Xu8, Jorge Enrique Tovar Perez, Maria L. Guevara, Qi Shen, Chaofeng Mu, Hui-Ying Tung, David B. Corry, Scott E. Evans, Xuewu Liu, Mauro Ferrari, Zhiqiang Zhang, Xian Chang Li, Rong-fu Wang, Haifa Shen
Micro- and nanometer-size particles have become popular candidates for cancer vaccine adjuvants. However, the mechanism by which such particles enhance immune responses remains unclear. Here, we report a porous silicon microparticle (PSM)-based cancer vaccine that greatly enhances cross-presentation and activates type I interferon (IFN-I) response in dendritic cells (DCs). PSM-loaded antigen exhibited prolonged early endosome localization and enhanced cross-presentation through both proteasome- and lysosome-dependent pathways. Phagocytosis of PSM by DCs induced IFN-I responses through a TRIF- and MAVS-dependent pathway. DCs primed with PSM-loaded HER2 antigen produced robust CD8 T cell-dependent anti-tumor immunity in mice bearing HER2+ mammary gland tumors. importantly, this vaccination activated the tumor immune microenvironment with elevated levels of intra-tumor IFN-I and MHCII expression, abundant CD11c+ DC infiltration, and tumor-specific cytotoxic T cell responses. These findings highlight the potential of PSM as an immune adjuvant to potentiate DC-based cancer immunotherapy.