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

  title={Structure of the 4-1BB/4-1BBL complex and distinct binding and functional properties of utomilumab and urelumab},
  author={S. M. Chin and C. R. Kimberlin and Z. Roe-Žur{\vz} and P. Zhang and A. Xu and S. Liao-Chan and Debasish Sen and Andrew R. Nager and N. S. Oakdale and C. Brown and Feng Wang and Y. Yang and K. Lindquist and Y. A. Yeung and S. Salek-Ardakani and J. Chaparro-Riggers},
  journal={Nature Communications},
  • S. M. Chin, C. R. Kimberlin, +13 authors J. Chaparro-Riggers
  • Published 2018
  • Medicine
  • Nature Communications
  • Abstract4-1BB (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… CONTINUE READING
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