Unexpected mechanisms of action for a cytokine receptor-blocking antibody.
Timothy R Hercus, Sophie E Broughton, Matthew P Hardy, Tracy L Nero, Nicholas J Wilson, Michael W Parker, Angel F Lopez
Mol Cell Oncol | Published : 2014
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.