Please use this identifier to cite or link to this item: http://scholarbank.nus.edu.sg/handle/10635/122565
Title: UNDERSTANDING THE MOLECULAR BASIS OF CELL DEATH MEDIATED BY ONCOSIS-INDUCING CYTOTOXIC ANTIBODIES
Authors: KOK YEE JIUN
Keywords: cytotoxic antibodies, cancer cells, oncosis, H type 1, ERM, membrane detachment
Issue Date: 14-Aug-2015
Source: KOK YEE JIUN (2015-08-14). UNDERSTANDING THE MOLECULAR BASIS OF CELL DEATH MEDIATED BY ONCOSIS-INDUCING CYTOTOXIC ANTIBODIES. ScholarBank@NUS Repository.
Abstract: Monoclonal antibodies (mAbs) A2, B3 and B8, raised against human embryonic stem cells, were found to specifically induce oncosis in various cancer cell lines but not to corresponding normal cell lines. Characterization revealed that these mAbs recognized a glycan moiety structurally related to blood group H type-1 expressed on multiple glycoproteins on the plasma membrane. Mechanism of cytotoxicity was found to involve detachment of the plasma membrane from the underlying cytoskeleton through inactivation of ezrin, radixin and meosin, and perturbation to cytoskeleton organization through degradation of actin-associated paxillin, talin and alpha-actinin. The resultant membrane injury was likely exacerbated by the loss of myosin II activity necessary for membrane repair. Cytotoxicity also required crosslinking of surface glycoproteins by the mAbs as monovalent Fab fragments did not cause cell death. These mAbs are potential biotherapeutics as they bind a tumour-specific epitope and exhibit a direct cytotoxic effect on cancer cells.
URI: http://scholarbank.nus.edu.sg/handle/10635/122565
Appears in Collections:Ph.D Theses (Restricted)

Show full item record
Files in This Item:
File Description SizeFormatAccess SettingsVersion 
KokYJ.pdf7.04 MBAdobe PDF

RESTRICTED

NoneLog In

Page view(s)

39
checked on Jan 11, 2018

Download(s)

5
checked on Jan 11, 2018

Google ScholarTM

Check


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