免疫系统
免疫疗法
癌症研究
癌症免疫疗法
生物
获得性免疫系统
癌症
癌细胞
免疫学
遗传学
作者
Yuan Hou,Wen Jiang,Christina A. Von Roemeling,Yaqing Qie,Xiujie Liu,Yuanxin Chen,Yifan Wang,Robert E. Wharen,Kyuson Yun,Guojun Bu,Keith L. Knutson,Betty Y.S. Kim
标识
DOI:10.1038/nnano.2017.69
摘要
Tumour-targeted immunotherapy offers the unique advantage of specific tumouricidal effects with reduced immune-associated toxicity. However, existing platforms suffer from low potency, inability to generate long-term immune memory and decreased activities against tumour-cell subpopulations with low targeting receptor levels. Here we adopted a modular design approach that uses colloidal nanoparticles as substrates to create a multivalent bi-specific nanobioconjugate engager (mBiNE) to promote selective, immune-mediated eradication of cancer cells. By simultaneously targeting the human epidermal growth factor receptor 2 (HER2) expressed by cancer cells and pro-phagocytosis signalling mediated by calreticulin, the mBiNE stimulated HER2-targeted phagocytosis and produced durable antitumour immune responses against HER2-expressing tumours. Interestingly, although the initial immune activation mediated by the mBiNE was receptor dependent, the subsequent antitumour immunity also generated protective effects against tumour-cell populations that lacked the HER2 receptor. Thus, the mBiNE represents a new targeted, nanomaterial-immunotherapy platform to stimulate innate and adaptive immunity and promote a universal antitumour response.
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