Journal article
The Anti-Cancer IgM Monoclonal Antibody PAT-SM6 Binds with High Avidity to the Unfolded Protein Response Regulator GRP78
Z Rosenes, TD Mulhern, DM Hatters, LL Ilag, BE Power, C Hosking, F Hensel, GJ Howlett, YF Mok
Plos One | Published : 2012
Open access
Abstract
The monoclonal IgM antibody PAT-SM6 derived from human tumours induces apoptosis in tumour cells and is considered a potential anti-cancer agent. A primary target for PAT-SM6 is the unfolded protein response regulator GRP78, over-expressed externally on the cell surface of tumour cells. Small angle X-ray scattering (SAXS) studies of human GRP78 showed a two-domain dumbbell-shaped monomer, while SAXS analysis of PAT-SM6 revealed a saucer-shaped structure accommodating five-fold symmetry, consistent with previous studies of related proteins. Sedimentation velocity analysis of GRP78 and PAT-SM6 mixtures indicated weak complex formation characterized by dissociation constants in the high micromo..
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Funding Acknowledgements
This research was supported by the Australian Research Council (LP100100392) with additional support provided by Patrys Ltd. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.