Molecular mechanism of PD-1/PD-L1 blockade via anti-PD-L1 antibodies atezolizumab and durvalumab

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 co...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Hyun Tae Lee, Ju Yeon Lee, Heejin Lim, Sang Hyung Lee, Yu Jeong Moon, Hyo Jeong Pyo, Seong Eon Ryu, Woori Shin, Yong-Seok Heo
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/b9c8ef6cf5af47aca2205e92c9d3f1e9
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:b9c8ef6cf5af47aca2205e92c9d3f1e9
record_format	dspace
spelling	oai:doaj.org-article:b9c8ef6cf5af47aca2205e92c9d3f1e92021-12-02T11:40:51ZMolecular mechanism of PD-1/PD-L1 blockade via anti-PD-L1 antibodies atezolizumab and durvalumab10.1038/s41598-017-06002-82045-2322https://doaj.org/article/b9c8ef6cf5af47aca2205e92c9d3f1e92017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-06002-8https://doaj.org/toc/2045-2322Abstract 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 antigen-antibody 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.Hyun Tae LeeJu Yeon LeeHeejin LimSang Hyung LeeYu Jeong MoonHyo Jeong PyoSeong Eon RyuWoori ShinYong-Seok HeoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Hyun Tae Lee Ju Yeon Lee Heejin Lim Sang Hyung Lee Yu Jeong Moon Hyo Jeong Pyo Seong Eon Ryu Woori Shin Yong-Seok Heo Molecular mechanism of PD-1/PD-L1 blockade via anti-PD-L1 antibodies atezolizumab and durvalumab
description	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 antigen-antibody 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.
format	article
author	Hyun Tae Lee Ju Yeon Lee Heejin Lim Sang Hyung Lee Yu Jeong Moon Hyo Jeong Pyo Seong Eon Ryu Woori Shin Yong-Seok Heo
author_facet	Hyun Tae Lee Ju Yeon Lee Heejin Lim Sang Hyung Lee Yu Jeong Moon Hyo Jeong Pyo Seong Eon Ryu Woori Shin Yong-Seok Heo
author_sort	Hyun Tae Lee
title	Molecular mechanism of PD-1/PD-L1 blockade via anti-PD-L1 antibodies atezolizumab and durvalumab
title_short	Molecular mechanism of PD-1/PD-L1 blockade via anti-PD-L1 antibodies atezolizumab and durvalumab
title_full	Molecular mechanism of PD-1/PD-L1 blockade via anti-PD-L1 antibodies atezolizumab and durvalumab
title_fullStr	Molecular mechanism of PD-1/PD-L1 blockade via anti-PD-L1 antibodies atezolizumab and durvalumab
title_full_unstemmed	Molecular mechanism of PD-1/PD-L1 blockade via anti-PD-L1 antibodies atezolizumab and durvalumab
title_sort	molecular mechanism of pd-1/pd-l1 blockade via anti-pd-l1 antibodies atezolizumab and durvalumab
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/b9c8ef6cf5af47aca2205e92c9d3f1e9
work_keys_str_mv	AT hyuntaelee molecularmechanismofpd1pdl1blockadeviaantipdl1antibodiesatezolizumabanddurvalumab AT juyeonlee molecularmechanismofpd1pdl1blockadeviaantipdl1antibodiesatezolizumabanddurvalumab AT heejinlim molecularmechanismofpd1pdl1blockadeviaantipdl1antibodiesatezolizumabanddurvalumab AT sanghyunglee molecularmechanismofpd1pdl1blockadeviaantipdl1antibodiesatezolizumabanddurvalumab AT yujeongmoon molecularmechanismofpd1pdl1blockadeviaantipdl1antibodiesatezolizumabanddurvalumab AT hyojeongpyo molecularmechanismofpd1pdl1blockadeviaantipdl1antibodiesatezolizumabanddurvalumab AT seongeonryu molecularmechanismofpd1pdl1blockadeviaantipdl1antibodiesatezolizumabanddurvalumab AT woorishin molecularmechanismofpd1pdl1blockadeviaantipdl1antibodiesatezolizumabanddurvalumab AT yongseokheo molecularmechanismofpd1pdl1blockadeviaantipdl1antibodiesatezolizumabanddurvalumab
_version_	1718395541673476096

Molecular mechanism of PD-1/PD-L1 blockade via anti-PD-L1 antibodies atezolizumab and durvalumab

Ejemplares similares