Multivalent bi-specific nanobioconjugate engager for targeted cancer immunotherapy

Hengfeng Yuan, 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

Research output: Contribution to journalArticle

61 Scopus citations

Abstract

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.

Original languageEnglish (US)
JournalNature Nanotechnology
DOIs
StateE-pub ahead of print - May 1 2017

Keywords

  • Journal Article

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