UM  > 健康科學學院
Anti-tumor effects of a ‘human & mouse cross-reactive’ anti-ADAM17 antibody in a pancreatic cancer model in vivo
Ye J.1; Yuen S.M.1; Murphy G.2; Xie R.1; Kwok H.F.1
2017-12-15
Source PublicationEuropean Journal of Pharmaceutical Sciences
ISSN18790720 09280987
Volume110Pages:62-69
Abstract

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal types of tumor amongst all human cancers due to late diagnosis and resistant to treatment with chemotherapy and radiation. Preclinical and clinical studies have revealed that ErbB family for example epidermal growth factor receptor (EGFR) is a validated molecular target for pancreatic cancer prevention and therapy. The ErbB signaling cascade is regulated by a member of the ADAM (a disintegrin and metalloprotease) family, namely ADAM17, by enzymatic cleavage of precursor ligands into soluble cytokines and growth factors. Mouse genetic studies have demonstrated that ADAM17 is required for PDAC development. In this study, we evaluated the anti-tumor effects of A9(B8) IgG – the first specific ‘human and mouse cross-reactive’ ADAM17 inhibitory antibody on pancreatic malignant transformation. We found that inhibition of ADAM17 with A9(B8) IgG efficiently suppressed the shedding of ADAM17 substrates both in vivo and in vitro. Furthermore, we demonstrated that administration of A9(B8) IgG significantly suppressed motility in human pancreatic cancer cells and also significantly delayed tumorigenesis in the Pdx1Cre;Kras;Trp53 PDAC mouse model. Inhibition of ADAM17 with A9(B8) IgG particularly affected the progression of pre-invasive pancreatic lesions to advanced PDAC in mice. Taken together, the preclinical data presented here will provide a starting point for clinical applications of ADAM17 targeted therapy.

KeywordAdam17 Inhibitory Antibody Pancreatic Ductal Adenocarcinoma (Pdac) Targeted Therapy Tumorigenesis
DOI10.1016/j.ejps.2017.05.057
URLView the original
Indexed BySCI
WOS Research AreaPharmacology & Pharmacy
WOS SubjectPharmacology & Pharmacy
WOS IDWOS:000414696100008
Fulltext Access
Citation statistics
Cited Times [WOS]:3   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionFaculty of Health Sciences
Affiliation1.Universidade de Macau
2.University of Cambridge
Recommended Citation
GB/T 7714
Ye J.,Yuen S.M.,Murphy G.,et al. Anti-tumor effects of a ‘human & mouse cross-reactive’ anti-ADAM17 antibody in a pancreatic cancer model in vivo[J]. European Journal of Pharmaceutical Sciences,2017,110:62-69.
APA Ye J.,Yuen S.M.,Murphy G.,Xie R.,&Kwok H.F..(2017).Anti-tumor effects of a ‘human & mouse cross-reactive’ anti-ADAM17 antibody in a pancreatic cancer model in vivo.European Journal of Pharmaceutical Sciences,110,62-69.
MLA Ye J.,et al."Anti-tumor effects of a ‘human & mouse cross-reactive’ anti-ADAM17 antibody in a pancreatic cancer model in vivo".European Journal of Pharmaceutical Sciences 110(2017):62-69.
Related Services
Recommend this item
Bookmark
Usage statistics
Export to Endnote
Google Scholar
Similar articles in Google Scholar
[Ye J.]'s Articles
[Yuen S.M.]'s Articles
[Murphy G.]'s Articles
Baidu academic
Similar articles in Baidu academic
[Ye J.]'s Articles
[Yuen S.M.]'s Articles
[Murphy G.]'s Articles
Bing Scholar
Similar articles in Bing Scholar
[Ye J.]'s Articles
[Yuen S.M.]'s Articles
[Murphy G.]'s Articles
Terms of Use
No data!
Social Bookmark/Share
All comments (0)
No comment.
 

Items in the repository are protected by copyright, with all rights reserved, unless otherwise indicated.