Multivalent bi-specific nanobioconjugate engager for targeted cancer immunotherapy

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptive Immunity
  • Animals
  • Colloids
  • Drug Delivery Systems / methods*
  • Humans
  • Immunity, Innate
  • Immunotherapy / methods*
  • Mice, Inbred BALB C
  • Nanoconjugates / chemistry*
  • Neoplasms / immunology
  • Neoplasms / pathology
  • Neoplasms / therapy*
  • Receptor, ErbB-2 / immunology*
  • THP-1 Cells


  • Colloids
  • Nanoconjugates
  • ERBB2 protein, human
  • Receptor, ErbB-2