Evidence map›Paper›PMID 34972111›Full record

ArticlePloS one2021

Structural basis of HLX10 PD-1 receptor recognition, a promising anti-PD-1 antibody clinical candidate for cancer immunotherapy.

Hassan Issafras, Shilong Fan, Chi-Ling Tseng, Yunchih Cheng, Peihua Lin, Lisa Xiao, Yun-Ju Huang, Chih-Hsiang Tu, Ya-Chin Hsiao, Min Li and 11 more

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 6 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed, 6 pooled it
3.4field-weighted citation impact, top 5% 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

24 citing papers in PubMed, 6 syntheses or guidelines pooled it, 47 citations in OpenAlex.

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  5. Prevalence of asthma and allergic rhinitis in children exposed to pets: a meta-analysis.European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery · 2024
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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

21 authors at 2 institutions in 2 countries.

Hassan IssafrasHengenix Inc., Fremont, CA, United States of America.ORCID 0000-0002-3441-7379
Shilong FanNational Protein Science Facility, Tsinghua University, Beijing, China.
Chi-Ling TsengHanchorBio Inc., Ltd, Taipei, Taiwan.
Yunchih ChengHanchorBio Inc., Ltd, Taipei, Taiwan.
Peihua LinHengenix Inc., Fremont, CA, United States of America.
Lisa XiaoShanghai Henlius Biotech, Inc., Shanghai, P. R. China.
Yun-Ju HuangHanchorBio Inc., Ltd, Taipei, Taiwan.
Chih-Hsiang TuHanchorBio Inc., Ltd, Taipei, Taiwan.
Ya-Chin HsiaoHanchorBio Inc., Ltd, Taipei, Taiwan.
Min LiNational Protein Science Facility, Tsinghua University, Beijing, China.
Yen-Hsiao ChenHanchorBio Inc., Ltd, Taipei, Taiwan.
Chien-Hsin HoHanchorBio Inc., Ltd, Taipei, Taiwan.
Ou LiHengenix Inc., Fremont, CA, United States of America.
Yanling WangHengenix Inc., Fremont, CA, United States of America.
Sandra ChenAnwita Biosciences, San Carlos, CA, United States of America.
Zhenyu JiShanghai Henlius Biotech, Inc., Shanghai, P. R. China.
Eric ZhangShanghai Henlius Biotech, Inc., Shanghai, P. R. China.
Yi-Ting MaoHengenix Inc., Fremont, CA, United States of America.
Eugene LiuTaipei Medical University, Taipei, Taiwan.
Shumin YangShanghai Henlius Biotech, Inc., Shanghai, P. R. China.
Weidong JiangHengenix Inc., Fremont, CA, United States of America.
Tsinghua University · CNTaipei Medical University · TW

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Cancer immunotherapies, such as checkpoint blockade of programmed cell death protein-1 (PD-1), represents a breakthrough in cancer treatment, resulting in unprecedented results in terms of overall and progression-free survival. Discovery and development of novel anti PD-1 inhibitors remains a field of intense investigation, where novel monoclonal antibodies (mAbs) and novel antibody formats (e.g., novel isotype, bispecific mAb and low-molecular-weight compounds) are major source of future therapeutic candidates. HLX10, a fully humanized IgG4 monoclonal antibody against PD-1 receptor, increased functional activities of human T-cells and showed in vitro, and anti-tumor activity in several tumor models. The combined inhibition of PD-1/PDL-1 and angiogenesis pathways using anti-VEGF antibody may enhance a sustained suppression of cancer-related angiogenesis and tumor elimination. To elucidate HLX10's mode of action, we solved the structure of HLX10 in complex with PD-1 receptor. Detailed epitope analysis showed that HLX10 has a unique mode of recognition compared to the clinically approved PD1 antibodies Pembrolizumab and Nivolumab. Notably, HLX10's epitope was closer to Pembrolizumab's epitope than Nivolumab's epitope. However, HLX10 and Pembrolizumab showed an opposite heavy chain (HC) and light chain (LC) usage, which recognizes several overlapping amino acid residues on PD-1. We compared HLX10 to Nivolumab and Pembrolizumab and it showed similar or better bioactivity in vitro and in vivo, providing a rationale for clinical evaluation in cancer immunotherapy.

Indexed as

ImmunotherapyAngiogenesis InhibitorsAnimalsAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedBevacizumabCD4-Positive T-LymphocytesCell Line, TumorCell ProliferationEpithelial-Mesenchymal TransitionEpitopesHumansImmunoglobulin Fab FragmentsInterferon-gammaInterleukin-2LigandsAngiogenesis InhibitorsAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedBevacizumabEpitopesImmunoglobulin Fab FragmentsInterferon-gammaInterleukin-2LigandsNivolumabpembrolizumabProgrammed Cell Death 1 ReceptorVascular Endothelial Growth Factor A

Identifiers

PMID34972111
PMCPMC8719770
OpenAlexW4226366416

What OpenQuestion holds

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LicenceCC BY
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.