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Structure of the 4-1BB/4-1BBL complex and distinct binding and functional properties of utomilumab and urelumab.

Nat Commun. 2018; 
Chin S Michael,Kimberlin Christopher R,Roe-Zurz Zygy,Zhang Pamela,Xu Allison,Liao-Chan Sindy,Sen Debasish,Nager Andrew R,Oakdale Nicole Schirle,Brown Colleen,Wang Feng,Yang Yuting,Lindquist Kevin,Yeung Yik Andy,Salek-Ardakani Shahram,Chaparro-Riggers Ja
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Biochemicals A00674, Genscript, Piscataway, NJ) at 100 nM as the “Second Analyte” was injected for 2 min at 10 µL/min in all flow cells and dissociation was monitored for 3 min. Get A Quote

摘要

4-1BB (CD137, TNFRSF9) is an inducible costimulatory receptor expressed on activated T cells. Clinical trials of two agonist antibodies, utomilumab (PF-05082566) and urelumab (BMS-663513), are ongoing in multiple cancer indications, and both antibodies demonstrate distinct activities in the clinic. To understand these differences, we solved structures of the human 4-1BB/4-1BBL complex, the 4-1BBL trimer alone, and 4-1BB bound to utomilumab or urelumab. The 4-1BB/4-1BBL complex displays a unique interaction between receptor and ligand when compared with other TNF family members. Furthermore, our ligand-only structure differs from previously published data. Utomilumab, a ligand-blocking antibody... More

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