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 language | English (US) |
|---|---|
| Journal | Nature Nanotechnology |
| DOIs | |
| State | Accepted/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
Multivalent bi-specific nanobioconjugate engager for targeted cancer immunotherapy. / Yuan, Hengfeng; Jiang, Wen; von Roemeling, Christina A.; Qie, Yaqing; Liu, Xiujie; Chen, Yuanxin; Wang, Yifan; Wharen, Robert E.; Yun, Kyuson; Bu, Guojun D; Knutson, Keith L; Kim, Y S Betty.
In: Nature Nanotechnology, 01.05.2017.Research output: Contribution to journal › Article
}
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 D
AU - Knutson, Keith L
AU - Kim, Y S Betty
PY - 2017/5/1
Y1 - 2017/5/1
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
JO - Nature Nanotechnology
JF - Nature Nanotechnology
SN - 1748-3387
ER -