Molecular mechanism of PD-1/PD-L1 blockade via anti-PD-L1 antibodies atezolizumab and durvalumab
- Title
- Molecular mechanism of PD-1/PD-L1 blockade via anti-PD-L1 antibodies atezolizumab and durvalumab
- Author
- 류성언
- Keywords
- CELL LUNG-CANCER; MONOCLONAL-ANTIBODIES; BLADDER-CANCER; PROGRAMMED DEATH-1; CRYSTAL-STRUCTURE; IMMUNE-SYSTEM; PD-1; IMMUNOTHERAPY; NIVOLUMAB; THERAPY
- Issue Date
- 2017-07
- Publisher
- NATURE PUBLISHING GROUP
- Citation
- SCIENTIFIC REPORTS, v. 7, Article no. 5532
- Abstract
- In 2016 and 2017, monoclonal antibodies targeting PD-L1, including atezolizumab, durvalumab, and avelumab, were approved by the FDA for the treatment of multiple advanced cancers. And many other anti-PD-L1 antibodies are under clinical trials. Recently, the crystal structures of PD-L1 in complex with BMS-936559 and avelumab have been determined, revealing details of the antigenantibody interactions. However, it is still unknown how atezolizumab and durvalumab specifically recognize PD-L1, although this is important for investigating novel binding sites on PD-L1 targeted by other therapeutic antibodies for the design and improvement of anti-PD-L1 agents. Here, we report the crystal structures of PD-L1 in complex with atezolizumab and durvalumab to elucidate the precise epitopes involved and the structural basis for PD-1/PD-L1 blockade by these antibodies. A comprehensive comparison of PD-L1 interactions with anti-PD-L1 antibodies provides a better understanding of the mechanism of PD-L1 blockade as well as new insights into the rational design of improved anti-PD-L1 therapeutics.
- URI
- https://www.nature.com/articles/s41598-017-06002-8https://repository.hanyang.ac.kr/handle/20.500.11754/114828
- ISSN
- 2045-2322
- DOI
- 10.1038/s41598-017-06002-8
- Appears in Collections:
- COLLEGE OF ENGINEERING[S](공과대학) > BIOENGINEERING(생명공학과) > Articles
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- Molecular mechanism of PD-1 PD-L1 blockade via anti-PD-L1 antibodies atezolizumab and durvalumab.pdfDownload
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