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 D Bu, Keith L Knutson, Y S Betty Kim

Research output: Contribution to journalArticle

46 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
StateAccepted/In press - May 1 2017

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ASJC Scopus subject areas

  • Bioengineering
  • Atomic and Molecular Physics, and Optics
  • Biomedical Engineering
  • Materials Science(all)
  • Condensed Matter Physics
  • Electrical and Electronic Engineering

Cite this

Yuan, H., Jiang, W., von Roemeling, C. A., Qie, Y., Liu, X., Chen, Y., Wang, Y., Wharen, R. E., Yun, K., Bu, G. D., Knutson, K. L., & Kim, Y. S. B. (Accepted/In press). Multivalent bi-specific nanobioconjugate engager for targeted cancer immunotherapy. Nature Nanotechnology. https://doi.org/10.1038/nnano.2017.69