Evidence map›Paper›PMID 34290297›Full record

ArticleScientific reports2021

Selective activation of pro-anti-IL-1β antibody enhances specificity for autoinflammatory disorder therapy.

Wen-Wei Lin, Yun-Chi Lu, Bo-Cheng Huang, Chih-Hung Chuang, Yi-An Cheng, I-Ju Chen, Hui-Ju Liu, Kai-Wen Ho, Tzu-Yi Liao, En-Shuo Liu and 4 more

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
0.6field-weighted citation impact, top 33% 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

10 citing papers in PubMed, 14 citations in OpenAlex.

  1. Article
  2. Conditionally Activatable Antibody Platforms: Mechanisms, Modalities, and Clinical Translation Potential.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2026
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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

14 authors at 3 institutions in 1 country.

Wen-Wei LinDepartment of Laboratory Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
Yun-Chi LuDepartment of Biomedical and Environmental Biology, Kaohsiung Medical University, 100 Shih-Chuan 1st Road, Kaohsiung, 80708, Taiwan.
Bo-Cheng HuangInstitute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan.
Chih-Hung ChuangDrug Development and Value Creation Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan.
Yi-An ChengDepartment of Biomedical and Environmental Biology, Kaohsiung Medical University, 100 Shih-Chuan 1st Road, Kaohsiung, 80708, Taiwan.
I-Ju ChenDepartment of Biomedical and Environmental Biology, Kaohsiung Medical University, 100 Shih-Chuan 1st Road, Kaohsiung, 80708, Taiwan.
Hui-Ju LiuGraduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, 100 Shih-Chuan 1st Road, Kaohsiung, 80708, Taiwan.
Kai-Wen HoGraduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, 100 Shih-Chuan 1st Road, Kaohsiung, 80708, Taiwan.
Tzu-Yi LiaoGraduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, 100 Shih-Chuan 1st Road, Kaohsiung, 80708, Taiwan.
En-Shuo LiuDrug Development and Value Creation Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan.
Ting-Yi WuGraduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, 100 Shih-Chuan 1st Road, Kaohsiung, 80708, Taiwan.
Long-Sen ChangInstitute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan.
Shih-Ting HongGraduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, 100 Shih-Chuan 1st Road, Kaohsiung, 80708, Taiwan. gwu714@gmail.com.
Tian-Lu ChengGraduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, 100 Shih-Chuan 1st Road, Kaohsiung, 80708, Taiwan. tlcheng@kmu.edu.tw.
Kaohsiung Medical University · TWNational Sun Yat-sen University · TWKaohsiung Medical University Chung-Ho Memorial Hospital · TW

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Canakinumab is a fully human monoclonal antibody that specifically neutralizes human interleukin (IL)-1β and has been approved by the US Food and Drug Administration for treating different types of autoinflammatory disorders such as cryopyrin-associated periodic syndrome, tumor necrosis factor receptor-associated periodic syndrome and systemic juvenile idiopathic arthritis. However, long-term systemic neutralization of IL-1β by Canakinumab may cause severe adverse events such as serious upper respiratory tract infections and inflammation, thereby decreasing the quality of life of patients. Here, we used an IgG1 hinge as an Ab lock to cover the IL-1β-binding site of Canakinumab by linking with matrix metalloprotease 9 (MMP-9) substrate to generate pro-Canakinumab that can be specifically activated in the inflamed regions in autoinflammatory diseases to enhance the selectivity and safety of treatment. The Ab lock significantly inhibited the IL-1β-binding by 68-fold compared with Canakinumab, and MMP-9 completely restored the IL-1β neutralizing ability of pro-Canakinumab within 60 min and blocked IL-1β-downstream signaling and IL-1β-regulated genes (i.e., IL-6). It is expected that MMP-9 cleavable and efficient Ab lock will be able to significantly enhance the selective reaction of Canakinumab at the disease site and reduce the on-target toxicities of Canakinumab during systemic circulation, thereby showing potential for development to improve the safety and quality of life of patients with autoinflammatory disorders in the future.

Indexed as

A549 CellsAntibodies, Monoclonal, HumanizedArthritis, JuvenileBinding SitesCryopyrin-Associated Periodic SyndromesHEK293 CellsHumansInterleukin-1betaMatrix Metalloproteinase 9Antibodies, Monoclonal, HumanizedcanakinumabInterleukin-1betaMatrix Metalloproteinase 9

Identifiers

PMID34290297
PMCPMC8295355
OpenAlexW3183750680

What OpenQuestion holds

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LicenceCC BY
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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.