Department of Orthopedics, Zhongshan Hospital, Fudan University, 111 Yixueyuan Road, Xuhui, Shanghai, China.
Department of Neurosurgery, Mayo Clinic College of Medicine, 4500 San Pablo Road, Jacksonville, Florida 32224, USA.
Nat Nanotechnol. 2017 Aug;12(8):763-769. doi: 10.1038/nnano.2017.69. Epub 2017 May 1.
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.
肿瘤靶向免疫疗法具有特异性杀伤肿瘤的独特优势，同时减少了免疫相关的毒性。然而，现有的平台存在效力低、无法产生长期免疫记忆以及对靶向受体水平低的肿瘤细胞亚群活性降低等问题。在这里，我们采用了一种模块化设计方法，使用胶体纳米粒子作为基质来构建一种多价双特异性纳米生物偶联物结合物（mBiNE），以促进选择性的、免疫介导的癌细胞清除。通过同时靶向癌细胞表达的人表皮生长因子受体 2（HER2）和钙网蛋白介导的预吞噬信号，mBiNE 刺激了 HER2 靶向吞噬，并对表达 HER2 的肿瘤产生了持久的抗肿瘤免疫反应。有趣的是，尽管 mBiNE 介导的初始免疫激活是受体依赖性的，但随后的抗肿瘤免疫也对缺乏 HER2 受体的肿瘤细胞群体产生了保护作用。因此，mBiNE 代表了一种新的靶向、纳米材料免疫治疗平台，可以刺激先天和适应性免疫，并促进普遍的抗肿瘤反应。
