Evidence map›Paper›PMID 30892132›Full record

ArticlemAbs

Glycosylation-independent binding of monoclonal antibody toripalimab to FG loop of PD-1 for tumor immune checkpoint therapy.

Hongchuan Liu, Lijing Guo, Jing Zhang, Yuehua Zhou, Jinwei Zhou, Jian Yao, Hai Wu, Sheng Yao, Bo Chen, Yan Chai and 5 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in mAbs. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
47citing papers in PubMed, 2 pooled it
3.8field-weighted citation impact, top 6% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

47 citing papers in PubMed, 2 syntheses or guidelines pooled it, 65 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors at 3 institutions in 4 countries.

Hongchuan Liua Department of Antibody Discovery and Engineering , Shanghai Junshi Biosciences Co., Ltd , Shanghai , China.
Lijing Guob Institute of Physical Science and Information Technology , Anhui University , Hefei , China.
Jing Zhanga Department of Antibody Discovery and Engineering , Shanghai Junshi Biosciences Co., Ltd , Shanghai , China.
Yuehua Zhoua Department of Antibody Discovery and Engineering , Shanghai Junshi Biosciences Co., Ltd , Shanghai , China.
Jinwei Zhoua Department of Antibody Discovery and Engineering , Shanghai Junshi Biosciences Co., Ltd , Shanghai , China.
Jian Yaoa Department of Antibody Discovery and Engineering , Shanghai Junshi Biosciences Co., Ltd , Shanghai , China.ORCID 0000-0001-7293-7140
Hai Wua Department of Antibody Discovery and Engineering , Shanghai Junshi Biosciences Co., Ltd , Shanghai , China.
Sheng Yaoa Department of Antibody Discovery and Engineering , Shanghai Junshi Biosciences Co., Ltd , Shanghai , China.ORCID 0000-0001-7293-7140
Bo Chena Department of Antibody Discovery and Engineering , Shanghai Junshi Biosciences Co., Ltd , Shanghai , China.
Yan Chaid CAS Key Laboratory of Pathogenic Microbiology and Immunology , Institute of Microbiology, Chinese Academy of Sciences , Beijing , China.ORCID 0000-0002-1912-3620
Jianxun Qid CAS Key Laboratory of Pathogenic Microbiology and Immunology , Institute of Microbiology, Chinese Academy of Sciences , Beijing , China.
George F Gaod CAS Key Laboratory of Pathogenic Microbiology and Immunology , Institute of Microbiology, Chinese Academy of Sciences , Beijing , China.
Shuguang Tanb Institute of Physical Science and Information Technology , Anhui University , Hefei , China.ORCID 0000-0002-2599-4959
Hui Fenga Department of Antibody Discovery and Engineering , Shanghai Junshi Biosciences Co., Ltd , Shanghai , China.
Jinghua Yanb Institute of Physical Science and Information Technology , Anhui University , Hefei , China.
Bioscience Research · USCzech Academy of Sciences, Institute of Microbiology · CZUniversity of Science and Technology of China · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Monoclonal antibody (mAb)-based blockade of programmed cell death 1 (PD-1) or its ligand to enable antitumor T-cell immunity has been successful in treating multiple tumors. However, the structural basis of the binding mechanisms of the mAbs and PD-1 and the effects of glycosylation of PD-1 on mAb interaction are not well understood. Here, we report the complex structure of PD-1 with toripalimab, a mAb that is approved by China National Medical Products Administration as a second-line treatment for melanoma and is under multiple Phase 1-Phase 3 clinical trials in both China and the US. Our analysis reveals that toripalimab mainly binds to the FG loop of PD-1 with an unconventionally long complementarity-determining region 3 loop of the heavy chain, which is distinct from the known binding epitopes of anti-PD-1 mAbs with structural evidences. The glycan modifications of PD-1 could be observed in three potential N-linked glycosylation sites, while no substantial influences were detected to the binding of toripalimab. These findings benefit our understanding of the binding mechanisms of toripalimab to PD-1 and shed light for future development of biologics targeting PD-1. Atomic coordinates have been deposited in the Protein Data Bank under accession code 6JBT.

Indexed as

AnimalsAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedB7-H1 AntigenCell Line, TumorComplementarity Determining RegionsEpitopesGlycosylationHumansImmunotherapyMelanomaMiceMice, Inbred C57BLNeoplasms, ExperimentalProgrammed Cell Death 1 ReceptorProtein BindingAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedB7-H1 AntigenComplementarity Determining RegionsEpitopesPDCD1 protein, humanProgrammed Cell Death 1 Receptortoripalimabcomplex structureglycosylationPD-1Toripalimab

Identifiers

PMID30892132
PMCPMC6601540
OpenAlexW2923766093

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.