Journal article
Unexpected mechanisms of action for a cytokine receptor-blocking antibody
TR Hercus, SE Broughton, MP Hardy, TL Nero, NJ Wilson, MW Parker, AF Lopez
Molecular and Cellular Oncology | TAYLOR & FRANCIS INC | Published : 2014
Abstract
CSL362 is a humanized interleukin-3 (IL-3)-neutralizing monoclonal antibody with enhanced effector function that binds the α subunit of the IL-3 receptor (IL3Rα). The crystal structure of an IL3Rα:CSL362 complex shows that IL3Rα adopts “open” and “closed” conformations. CSL362 blocks IL-3 function through both IL3Rα conformations but via distinct and unexpected mechanisms.
Grants
Funding Acknowledgements
This work was supported by grants from the National Health and Medical Research Council (NHMRC) of Australia, from Cancer Australia and from the Australian Cancer Research Foundation. Funding from the Victorian Government Operational Infrastructure Support Scheme to St Vincent's Institute is acknowledged. MWP is an NHMRC Research Fellow and SEB is a Postdoctoral Fellow supported by the Leukaemia Foundation of Australia.