UM  > Faculty of Health Sciences
Antibody targeting of Cathepsin S induces antibody-dependent cellular cytotoxicity
Kwok H.F.2; Buick R.J.2; Kuehn D.2; Gormley J.A.2; Doherty D.2; Jaquin T.J.2; McClurg A.2; Ward C.2; Byrne T.2; Jaworski J.2; Leung K.L.2; Snoddy P.2; McAnally C.2; Burden R.E.2; Gray B.2; Lowry J.2; Sermadiras I.2; Gruszka N.2; Courtenay-Luck N.2; Kissenpfennig A.1; Scott C.J.1; Johnston J.A.2; Olwill S.A.2
2011-12-14
Source PublicationMolecular Cancer
ISSN14764598
Volume10
Abstract

Background: Proteolytic enzymes have been implicated in driving tumor progression by means of their cancer cell microenvironment activity where they promote proliferation, differentiation, apoptosis, migration, and invasion. Therapeutic strategies have focused on attenuating their activity using small molecule inhibitors, but the association of proteases with the cell surface during cancer progression opens up the possibility of targeting these using antibody dependent cellular cytotoxicity (ADCC). Cathepsin S is a lysosomal cysteine protease that promotes the growth and invasion of tumour and endothelial cells during cancer progression. Our analysis of colorectal cancer patient biopsies shows that cathepsin S associates with the cell membrane indicating a potential for ADCC targeting.Results: Here we report the cell surface characterization of cathepsin S and the development of a humanized antibody (Fsn0503h) with immune effector function and a stable in vivo half-life of 274 hours. Cathepsin S is expressed on the surface of tumor cells representative of colorectal and pancreatic cancer (23%-79% positive expression). Furthermore the binding of Fsn0503h to surface associated cathepsin S results in natural killer (NK) cell targeted tumor killing. In a colorectal cancer model Fsn0503h elicits a 22% cytotoxic effect.Conclusions: This data highlights the potential to target cell surface associated enzymes, such as cathepsin S, as therapeutic targets using antibodies capable of elicitingADCC in tumor cells. © 2011 Kwok et al; licensee BioMed Central Ltd.

KeywordAdcc Antibody Cathepsin s Microenvironment Protease
DOI10.1186/1476-4598-10-147
URLView the original
Indexed BySCI
Language英语
WOS Research AreaBiochemistry & Molecular Biology ; Oncology
WOS SubjectBiochemistry & Molecular Biology ; Oncology
WOS IDWOS:000300361100001
Fulltext Access
Citation statistics
Cited Times [WOS]:13   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionFaculty of Health Sciences
Affiliation1.Queen's University Belfast
2.Fusion Antibodies plc
Recommended Citation
GB/T 7714
Kwok H.F.,Buick R.J.,Kuehn D.,et al. Antibody targeting of Cathepsin S induces antibody-dependent cellular cytotoxicity[J]. Molecular Cancer,2011,10.
APA Kwok H.F..,Buick R.J..,Kuehn D..,Gormley J.A..,Doherty D..,...&Olwill S.A..(2011).Antibody targeting of Cathepsin S induces antibody-dependent cellular cytotoxicity.Molecular Cancer,10.
MLA Kwok H.F.,et al."Antibody targeting of Cathepsin S induces antibody-dependent cellular cytotoxicity".Molecular Cancer 10(2011).
Files in This Item:
There are no files associated with this item.
Related Services
Recommend this item
Bookmark
Usage statistics
Export to Endnote
Google Scholar
Similar articles in Google Scholar
[Kwok H.F.]'s Articles
[Buick R.J.]'s Articles
[Kuehn D.]'s Articles
Baidu academic
Similar articles in Baidu academic
[Kwok H.F.]'s Articles
[Buick R.J.]'s Articles
[Kuehn D.]'s Articles
Bing Scholar
Similar articles in Bing Scholar
[Kwok H.F.]'s Articles
[Buick R.J.]'s Articles
[Kuehn D.]'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.