Anti-Tumour Effects of a Human & Mouse Cross-Reactive’ Anti-ADAM17 Antibody in a Pancreatic Cancer Model In Vivo

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	Anti-Tumour Effects of a Human & Mouse Cross-Reactive’ Anti-ADAM17 Antibody in a Pancreatic Cancer Model In Vivo
	Yuen, S. M.; Ye, J.; Murphy, G.; Xie, R.; Kwok, H. F.
	2016-08-23
Source Publication	: Emerging Technologies in Drug Discovery and Development
Pages	28-28
Publisher	International Association of Physical Chemists
Abstract	TNF-Alpha Converting Enzyme (TACE) is a membrane-bound zinc metalloprotease (MP) that may play a significant role in tumour biology, notably by the conversion of many inactive cell-surface ligands into active soluble ligands; e.g. ErbB-ligands such as TGF-Alpha, HB-EGF, EGF, Amphiregulin and Epigen. Moreover, TACE can stimulate local inflammation by solubilising TNF-Alpha, and aid immunological evasion by removing tumour cell surface MICA. Due to the homology between MP active sites, the development of small molecule TACE inhibitors has been plagued with unwanted non-specific MP activity. Recently, our group has successfully developed an inhibitory TACE antibody [A9(B8)] and showed the effective inhibition of both human and mouse TACE. In this study, we evaluated anti-tumour efficacy of A9(B8) -- the first specific ‘Human and Mouse Cross-Reactive’ anti-ADAM17 inhibitory IgG antibody with a mouse model of pancreatic ductal adenocarcinoma (PDA). It has been demonstrated that ADAM17 is required for Kras-deriven tumorigenesis in PDA mouse models. Here, we show that intraperitoneal injection of A9(B8) effectively attenuates high grade pancreatic intraepithelial neoplasisa (PanIN) formation in Pdx1Cre;KrasG12D;Trp53fl/+ mice. Thus, A9(B8) has anti-ADAM17 activity in vivo, inhibits pa
Keyword	TACE TNF-Alpha Anti-ADAM17 Antibody Pancreatic Mouse Model
URL	View the original
Language	英語English
The Source to Article	PB_Publication
PUB ID	23097
Document Type	Conference paper
Collection	DEPARTMENT OF BIOMEDICAL SCIENCES
Corresponding Author	Xie, R.; Kwok, H. F.
Recommended Citation GB/T 7714	Yuen, S. M.,Ye, J., Murphy, G.,et al. Anti-Tumour Effects of a Human & Mouse Cross-Reactive’ Anti-ADAM17 Antibody in a Pancreatic Cancer Model In Vivo[C]:International Association of Physical Chemists, 2016, 28-28.
APA	Yuen, S. M.., Ye, J.., Murphy, G.., Xie, R.., & Kwok, H. F. (2016). Anti-Tumour Effects of a Human & Mouse Cross-Reactive’ Anti-ADAM17 Antibody in a Pancreatic Cancer Model In Vivo. : Emerging Technologies in Drug Discovery and Development, 28-28.

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