Selection of a picomolar antibody that targets CXCR2-mediated neutrophil activation and alleviates EAE symptoms
2021-05-05
发表期刊NATURE COMMUNICATIONS (IF:14.7[JCR-2023],16.1[5-Year])
ISSN2041-1723
发表状态已发表
DOI10.1038/s41467-021-22810-z
摘要

Receptors and their ligands are important therapeutic targets for about one third of
marketed drugs. We describe here an epitope-guided approach for selection of novel
antibodies that modulate cellular signaling of targeted receptors. We chose CXC
chemokine receptor 2 (CXCR2) in the G-protein coupled receptor superfamily as
receptor and a CXCR2 N-terminal peptide for antibody selection. We obtain a highly
selective, tight-binding antibody from a 1011-member antibody library using
combinatorial enrichment. Structural and Hydrogen-Deuterium-Exchange mass
spectrometry analyses demonstrate antibody interaction with an N-terminal region of
CXCR2 that is part of the interleukin-8 epitope. The antibody strongly inhibits
interleukin-8-induced and CXCR2-mediated neutrophil chemotaxis in vitro and
alleviates the hCXCR2-dependent Experimental Autoimmune Encephalomyelitis
symptoms in vivo. Inappropriate neutrophil migration accompanies many diseases
including inflammatory bowel disease, glomerulonephritis, allergic asthma, chronic
obstructive pulmonary disease, and cancer. Thus, this potent new antibody has potential
for development as a therapeutic agent, akin to anti-TNF antibodies. However, an
important difference here is that the antibody targets the chemokine receptor and
competes with natural ligand, rather than targeting the ligand itself.

学科领域生物学
学科门类理学
收录类别SCI ; SCIE
WOS记录号WOS:000656480900014
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文献类型期刊论文
条目标识符https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/126132
专题免疫化学研究所
生命科学与技术学院_PI研究组_陈佳组
免疫化学研究所_特聘教授组_功能筛选实验室
免疫化学研究所_特聘教授组_抗体设计学实验室
生命科学与技术学院_硕士生
生命科学与技术学院_博士生
免疫化学研究所_PI研究组_杨贝组
生命科学与技术学院_PI研究组_李扬扬组
共同第一作者Yue Wan; Nan Wang; Jiangchao Xiang
通讯作者Guang Yang; Richard A. Lerner
作者单位
1.Shanghai Institute for Advanced Immunochemical Studies, ShanghaiTech University, Shanghai 201210, China.
2.School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China.
3.University of Chinese Academy of Sciences, Beijing 100049, China
4.University of Chinese Academy of Sciences, Beijing 100049, China
5.Department of Chemistry, The Scripps Research Institute, La Jolla, CA 92037, USA.
6.Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, California 92037, USA
7.The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, California 92037, USA
第一作者单位免疫化学研究所
通讯作者单位免疫化学研究所
第一作者的第一单位免疫化学研究所
推荐引用方式
GB/T 7714
Xiaojie Shi,Yue Wan,Nan Wang,et al. Selection of a picomolar antibody that targets CXCR2-mediated neutrophil activation and alleviates EAE symptoms[J]. NATURE COMMUNICATIONS,2021.
APA Xiaojie Shi.,Yue Wan.,Nan Wang.,Jiangchao Xiang.,Tao Wang.,...&Richard A. Lerner.(2021).Selection of a picomolar antibody that targets CXCR2-mediated neutrophil activation and alleviates EAE symptoms.NATURE COMMUNICATIONS.
MLA Xiaojie Shi,et al."Selection of a picomolar antibody that targets CXCR2-mediated neutrophil activation and alleviates EAE symptoms".NATURE COMMUNICATIONS (2021).
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