Crystal clear: visualizing the intervention mechanism of the PD-1/PD-L1 interaction by two cancer therapeutic monoclonal antibodies.
10.1007/s13238-016-0337-7
- Author:
Shuguang TAN
1
;
Danqing CHEN
1
;
Kefang LIU
2
;
Mengnan HE
1
;
Hao SONG
3
;
Yi SHI
1
;
Jun LIU
2
;
Catherine W-H ZHANG
4
;
Jianxun QI
1
;
Jinghua YAN
1
;
Shan GAO
5
;
George F GAO
6
Author Information
1. CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100101, China.
2. National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention (China CDC), Beijing, 102206, China.
3. Research Network of Immunity and Health (RNIH), Beijing Institutes of Life Science, Chinese Academy of Sciences, Beijing, 100101, China.
4. ImmuFucell Biotechnology Co.Ltd., Beijing, 100102, China.
5. CAS Key Laboratory of Bio-medical Diagnostics, Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou, Jiangsu, 215163, China. gaos@sibet.ac.cn.
6. CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100101, China. gaof@im.ac.cn.
- Publication Type:Journal Article
- Keywords:
PD-1/PD-L1 interaction;
checkpoint blockade;
molecular basis;
therapeutic antibody
- MeSH:
Antibodies, Monoclonal;
immunology;
therapeutic use;
Antibodies, Monoclonal, Humanized;
immunology;
therapeutic use;
B7-H1 Antigen;
antagonists & inhibitors;
immunology;
Humans;
Neoplasms;
drug therapy;
immunology;
pathology;
Programmed Cell Death 1 Receptor;
antagonists & inhibitors;
immunology;
Signal Transduction;
drug effects;
immunology;
T-Lymphocytes;
immunology
- From:
Protein & Cell
2016;7(12):866-877
- CountryChina
- Language:English
-
Abstract:
Antibody-based PD-1/PD-L1 blockade therapies have taken center stage in immunotherapies for cancer, with multiple clinical successes. PD-1 signaling plays pivotal roles in tumor-driven T-cell dysfunction. In contrast to prior approaches to generate or boost tumor-specific T-cell responses, antibody-based PD-1/PD-L1 blockade targets tumor-induced T-cell defects and restores pre-existing T-cell function to modulate antitumor immunity. In this review, the fundamental knowledge on the expression regulations and inhibitory functions of PD-1 and the present understanding of antibody-based PD-1/PD-L1 blockade therapies are briefly summarized. We then focus on the recent breakthrough work concerning the structural basis of the PD-1/PD-Ls interaction and how therapeutic antibodies, pembrolizumab targeting PD-1 and avelumab targeting PD-L1, compete with the binding of PD-1/PD-L1 to interrupt the PD-1/PD-L1 interaction. We believe that this structural information will benefit the design and improvement of therapeutic antibodies targeting PD-1 signaling.
