Unexpected mechanisms of action for a cytokine receptor-blocking antibody

Timothy R Hercus1, Sophie E Broughton2, Matthew P Hardy3

  • 1The Centre for Cancer Biology; SA Pathology and the University of South Australia ; Adelaide, South Australia.

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.

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