Evidence map›Paper›PMID 32073836›Full record

ArticleACS sensors2020

Digital Receptor Occupancy Assay in Quantifying On- and Off-Target Binding Affinities of Therapeutic Antibodies.

Chao-Kai Chou, Yen-Liang Liu, Yuan-I Chen, Po-Jung Huang, Pei-Hsiang Tsou, Chun-Te Chen, Heng-Huan Lee, Ying-Nai Wang, Jennifer L Hsu, Jin-Fong Lee and 4 more

Abstract read
In one paragraph

Article in ACS sensors, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
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

2 citing papers in PubMed.

  1. Article
  2. Article
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.

Chao-Kai ChouDepartment of Molecular and Cellular Oncology , The University of Texas MD Anderson Cancer Center , Houston , Texas 77030 , United States.
Yen-Liang LiuGraduate Institute of Biomedical Sciences , China Medical University , Taichung , Taiwan 40402.ORCID 0000-0002-1635-4335
Yuan-I ChenDepartment of Biomedical Engineering , The University of Texas at Austin , Austin , Texas 78712 , United States.
Po-Jung HuangDepartment of Materials Science and Engineering , Texas A&M University , College Station , Texas 77840 , United States.ORCID 0000-0003-1273-3060
Pei-Hsiang TsouDepartment of Molecular and Cellular Oncology , The University of Texas MD Anderson Cancer Center , Houston , Texas 77030 , United States.
Chun-Te ChenDepartment of Molecular and Cellular Oncology , The University of Texas MD Anderson Cancer Center , Houston , Texas 77030 , United States.
Heng-Huan LeeDepartment of Molecular and Cellular Oncology , The University of Texas MD Anderson Cancer Center , Houston , Texas 77030 , United States.
Ying-Nai WangDepartment of Molecular and Cellular Oncology , The University of Texas MD Anderson Cancer Center , Houston , Texas 77030 , United States.
Jennifer L HsuDepartment of Molecular and Cellular Oncology , The University of Texas MD Anderson Cancer Center , Houston , Texas 77030 , United States.
Jin-Fong LeeDepartment of Molecular and Cellular Oncology , The University of Texas MD Anderson Cancer Center , Houston , Texas 77030 , United States.
Thomas E YankeelovDepartment of Biomedical Engineering , The University of Texas at Austin , Austin , Texas 78712 , United States.
Jun KameokaDepartment of Materials Science and Engineering , Texas A&M University , College Station , Texas 77840 , United States.
Hsin-Chih YehDepartment of Biomedical Engineering , The University of Texas at Austin , Austin , Texas 78712 , United States.ORCID 0000-0001-6654-5626
Mien-Chie HungDepartment of Molecular and Cellular Oncology , The University of Texas MD Anderson Cancer Center , Houston , Texas 77030 , United States.

Funding

Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Fabien Delerue · 1985 to 2026
$290.8M
Mechanical Drugs: Harnessing Cancer Aggressiveness to Overcome Its ResistanceU01CA201777 · NCI · MASIMO CORPORATION · PI NAULI, SURYA, SHARMA, VIKRANT · 2016 to 2020
$2.4M
Rational Combination Therapy with PARP Inhibitors in Triple Negative Breast CancerR01CA211615 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI YANG, LIUQING · 2017 to 2021
$2.1M
Training Grant in Cancer BiologyT32CA186892 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI KALLURI, RAGHU · 2016 to 2020
$1.1M
Turning a sequence barcode into a spectral barcode for single-cell analysis.R21GM129617 · NIGMS · UNIVERSITY OF TEXAS AT AUSTIN · PI FINKELSTEIN, ILYA J, YEH, HSIN-CHIH · 2019 to 2020
$398k
NCI NIH HHS P30 CA016672NCI NIH HHS R01 CA211615NCI NIH HHS T32 CA186892NCI NIH HHS U01 CA201777NIGMS NIH HHS R21 GM129617
6 · The paper itself

Abstract

While monoclonal antibodies are the fastest-growing class of therapeutic agents, we lack a method that can directly quantify the on- and off-target binding affinities of newly developed therapeutic antibodies in crude cell lysates. As a result, some therapeutic antibody candidates could have a moderate on-target binding affinity but a high off-target binding affinity, which not only gives a reduced efficacy but triggers unwanted side effects. Here, we report a single-molecule counting method that precisely quantifies antibody-bound receptors, free receptors, and unbound antibodies in crude cell lysates, termed digital receptor occupancy assay (DRO). Compared to the traditional flow cytometry-based binding assay, DRO assay enables direct and digital quantification of the three molecular species in solution without the additional antibodies for competitive binding. When characterizing the therapeutic antibody, cetuximab, using DRO assay, we found the on-target binding ratio to be 65% and the binding constant (

Indexed as

AnimalsAntibodiesAntibody AffinityHumansMiceAntibodiesantibody binding affinitymicrofluidicson-target bindingon-target quantificationreceptor occupancysingle-molecule detection

Identifiers

PMID32073836
PMCPMC7093205

What OpenQuestion holds

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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.