Unexpected mechanisms of action for a cytokine receptor-blocking antibody.
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.
The Centre for Cancer Biology; SA Pathology and the University of South Australia ; Adelaide, South Australia.
Timothy R
TR
Hercus
Australian Cancer Research Foundation Rational Drug Discovery Centre; St. Vincent's Institute of Medical Research ; Fitzroy, Victoria.
Sophie E
SE
Broughton
CSL Limited ; Parkville, Victoria.
Matthew P
MP
Hardy
Australian Cancer Research Foundation Rational Drug Discovery Centre; St. Vincent's Institute of Medical Research ; Fitzroy, Victoria.
Tracy L
TL
Nero
CSL Limited ; Parkville, Victoria.
Nicholas J
NJ
Wilson
Australian Cancer Research Foundation Rational Drug Discovery Centre; St. Vincent's Institute of Medical Research; Fitzroy, Victoria; Department of Biochemistry and Molecular Biology; Bio21 Molecular Science and Biotechnology Institute; University of Melbourne; Parkville, Victoria, Australia.
Michael W
MW
Parker
The Centre for Cancer Biology; SA Pathology and the University of South Australia ; Adelaide, South Australia.
Angel F
AF
Lopez
antibodies; cancer; cytokine receptor; signaling