Evidence map›Paper›PMID 37954614›Full record

ArticleFrontiers in immunology2023

A novel nanobody-based HER2-targeting antibody exhibits potent synergistic antitumor efficacy in trastuzumab-resistant cancer cells.

Xinlin Liu, Linli Luan, Xi Liu, Dingwen Jiang, Junwen Deng, Jiazhen Xu, Yang Yuan, Jiyao Xing, Bingguan Chen, Dongming Xing and 1 more

Open access · goldAbstract read
In one paragraph

Article in Frontiers in immunology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed, 1 pooled it
4.6field-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

12 citing papers in PubMed, 1 synthesis or guideline pooled it, 20 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

11 authors at 1 institution in 1 country.

Xinlin LiuThe Affiliated Hospital of Qingdao University, Qingdao University, Qingdao, China.
Linli LuanNoventi Biopharmaceuticals Co., Ltd, Shanghai, China.
Xi LiuBioworkshops (Suzhou) Limited, Souzhou, China.
Dingwen JiangNoventi Biopharmaceuticals Co., Ltd, Shanghai, China.
Junwen DengThe Affiliated Hospital of Qingdao University, Qingdao University, Qingdao, China.
Jiazhen XuThe Affiliated Hospital of Qingdao University, Qingdao University, Qingdao, China.
Yang YuanThe Affiliated Hospital of Qingdao University, Qingdao University, Qingdao, China.
Jiyao XingThe Affiliated Hospital of Qingdao University, Qingdao University, Qingdao, China.
Bingguan ChenNoventi Biopharmaceuticals Co., Ltd, Shanghai, China.
Dongming XingThe Affiliated Hospital of Qingdao University, Qingdao University, Qingdao, China.
Haiming HuangNoventi Biopharmaceuticals Co., Ltd, Shanghai, China.
Qingdao University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Human epithelial growth factor receptor-2 (HER2) plays an oncogenic role in numerous tumors, including breast, gastric, and various other solid tumors. While anti-HER2 therapies are approved for the treatment of HER2-positive tumors, a necessity persists for creating novel HER2-targeted agents to resolve therapeutic resistance. Utilizing a synthetic nanobody library and affinity maturation, our study identified four anti-HER2 nanobodies that exhibited high affinity and specificity. These nanobodies recognized three distinct epitopes of HER2-ECD. Additionally, we constructed VHH-Fc and discovered that they facilitated superior internalization and showed moderate growth inhibition. Compared to the combination of trastuzumab and pertuzumab, the VHH-Fc combos or their combination with trastuzumab demonstrated greater or comparable antitumor activity in both ligand-independent and ligand-driven tumors. Most remarkably, A9B5-Fc, which targeted domain I of HER2-ECD, displayed significantly enhanced trastuzumab-synergistic antitumor efficacy compared to pertuzumab under trastuzumab-resistant conditions. Our findings offer anti-HER2 nanobodies with high affinity and non-overlapping epitope recognition. The novel nanobody-based HER2-targeted antibody, A9B5-Fc, binding to HER2-ECD I, mediates promising receptor internalization. It possesses the potential to serve as a potent synergistic partner with trastuzumab, contributing to overcoming acquired resistance.

Indexed as

NeoplasmsSingle-Domain AntibodiesEpitopesErb-b2 Receptor Tyrosine KinasesHumansLigandsTrastuzumabEpitopesErb-b2 Receptor Tyrosine KinasesLigandsSingle-Domain AntibodiesTrastuzumabFc fusionHER2ligand-dependent heterodimerizationnanobodysynergistic efficacytrastuzumab-resistance

Identifiers

PMID37954614
PMCPMC10634241
OpenAlexW4388267116

What OpenQuestion holds

Textmetadata
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.