TY - JOUR
T1 - Multivalent bi-specific nanobioconjugate engager for targeted cancer immunotherapy
AU - Yuan, Hengfeng
AU - Jiang, Wen
AU - Von Roemeling, Christina A.
AU - Qie, Yaqing
AU - Liu, Xiujie
AU - Chen, Yuanxin
AU - Wang, Yifan
AU - Wharen, Robert E.
AU - Yun, Kyuson
AU - Bu, Guojun
AU - Knutson, Keith L.
AU - Kim, Betty Y.S.
N1 - Publisher Copyright:
© 2017 Macmillan Publishers Limite.
PY - 2017/8/1
Y1 - 2017/8/1
N2 - 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.
AB - 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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U2 - 10.1038/nnano.2017.69
DO - 10.1038/nnano.2017.69
M3 - Article
C2 - 28459470
AN - SCOPUS:85018454897
SN - 1748-3387
VL - 12
SP - 763
EP - 769
JO - Nature Nanotechnology
JF - Nature Nanotechnology
IS - 8
ER -