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Tislelizumab uniquely binds to the CC′ loop of PD‐1 with slow‐dissociated rate and complete PD‐L1 blockage
- Source :
- FEBS Open Bio, Vol 11, Iss 3, Pp 782-792 (2021)
- Publication Year :
- 2021
- Publisher :
- Wiley, 2021.
-
Abstract
- Programmed cell death protein 1 (PD‐1), an immune checkpoint receptor expressed by activated T, B, and NK cells, is a well‐known target for cancer immunotherapy. Tislelizumab (BGB‐A317) is an anti‐PD‐1 antibody that has recently been approved for treatment of Hodgkin's lymphoma and urothelial carcinoma. Here, we show that tislelizumab displayed remarkable antitumor efficacy in a B16F10/GM‐CSF mouse model. Structural biology and Surface plasmon resonance (SPR) analyses revealed unique epitopes of tislelizumab, and demonstrated that the CC′ loop of PD‐1, a region considered to be essential for binding to PD‐1 ligand 1 (PD‐L1) but not reported as targeted by other therapeutic antibodies, significantly contributes to the binding of tislelizumab. The binding surface of tislelizumab on PD‐1 overlaps largely with that of the PD‐L1. SPR analysis revealed the extremely slow dissociation rate of tislelizumab from PD‐1. Both structural and functional analyses align with the observed ability of tislelizumab to completely block PD‐1/PD‐L1 interaction, broadening our understanding of the mechanism of action of anti‐PD‐1 antibodies.
Details
- Language :
- English
- ISSN :
- 22115463
- Volume :
- 11
- Issue :
- 3
- Database :
- Directory of Open Access Journals
- Journal :
- FEBS Open Bio
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.7566c20ed34c4efea2984437bc6264ed
- Document Type :
- article
- Full Text :
- https://doi.org/10.1002/2211-5463.13102