Health AI Central
Peer-Reviewed Publication
Nat Commun2023;14(1):7940.December 1, 2023Journal Article

Structural basis of antibody inhibition and chemokine activation of the human CC chemokine receptor 8.

Dawei Sun1, Yonglian Sun2, Eric Janezic3, Tricia Zhou3, Matthew Johnson1, Caleigh Azumaya1, Sigrid Noreng1,4, Cecilia Chiu2, Akiko Seki5,6, Teresita L Arenzana5,7, John M Nicoludis1, Yongchang Shi3, Baomei Wang5, Hoangdung Ho1, Prajakta Joshi8, Christine Tam8, Jian Payandeh1,9, Laëtitia Comps-Agrar3, Jianyong Wang3, Sascha Rutz10, James T Koerber11, Matthieu Masureel12
1Department of Structural Biology, Genentech Inc., South San Francisco, CA, 94080, USA.
2Department of Antibody Engineering, Genentech Inc., South San Francisco, CA, 94080, USA.
3Department of Biochemical and Cellular Pharmacology, Genentech Inc., South San Francisco, CA, 94080, USA.
4Septerna Inc., South San Francisco, CA, 94080, USA.
5Department of Cancer Immunology, Genentech Inc., South San Francisco, CA, 94080, USA.
6Tune Therapeutics, Durham, NC, 27701, USA.
7HIBio, South San Francisco, CA, 94080, USA.
8Department of Biomolecular Resources, Genentech Inc., South San Francisco, CA, 94080, USA.
9Exelixis Inc., Alameda, CA, 94502, USA.
10Department of Cancer Immunology, Genentech Inc., South San Francisco, CA, 94080, USA. rutz.sascha@gene.com.
11Department of Antibody Engineering, Genentech Inc., South San Francisco, CA, 94080, USA. koerber.james@gene.com.
12Department of Structural Biology, Genentech Inc., South San Francisco, CA, 94080, USA. masureel.matthieu@gene.com.
PubMed PMC DOI PDF

Abstract

The C-C motif chemokine receptor 8 (CCR8) is a class A G-protein coupled receptor that has emerged as a promising therapeutic target in cancer. Targeting CCR8 with an antibody has appeared to be an attractive therapeutic approach, but the molecular basis for chemokine-mediated activation and antibody-mediated inhibition of CCR8 are not fully elucidated. Here, we obtain an antagonist antibody again…

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