scholarly journals A competitive ligand-binding assay for the detection of neutralizing antibodies against dostarlimab (TSR-042)

AAPS Open ◽  
2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Xiaolong Tom Zhang ◽  
Hong Chen ◽  
Weiping Shao ◽  
Zhongping John Lin ◽  
Murad Melhem ◽  
...  
Keyword(s):  
Ligand Binding ◽  
Human Serum ◽  
Neutralizing Antibodies ◽  
Binding Assay ◽  
False Positive Rate ◽  
Ligand Binding Assay ◽  
Drug Interference ◽  
Hook Effect ◽  
System Suitability ◽  
Competitive Ligand

AbstractDostarlimab is a humanized anti–PD-1 monoclonal antibody. Dostarlimab (JEMPERLI; TSR-042) was recently approved in the USA and in the EU. The presence of neutralizing antibodies (NAbs) is a cause for concern because they block the therapeutic function of the antibody and reduce drug efficacy. Therefore, programs developing therapeutic biologics need to develop and validate assays that adequately assess the presence of NAbs in the serum of patients treated with biologic therapies. Presented here is the development and validation of a competitive ligand-binding assay that specifically detects anti-dostarlimab NAbs in human serum. Precision, sensitivity, hook effect, selectivity, assay robustness, stabilities, and system suitability were evaluated. In addition, drug tolerance of the assay with the implementation of a drug removal process was investigated. The cut point factor for the detection of NAbs in human serum at a 1% false-positive rate was determined. The assay’s precision, sensitivity, hook effect, selectivity, robustness, and drug interference were tested and found to be acceptable. With system suitability and stability established, this assay has been used to evaluate NAbs to guide the development of dostarlimab.Trial registration: Clinicaltrials.gov, NCT02715284. Registered 9 March 2016

Comparison of competitive ligand-binding assay and bioassay formats for the measurement of neutralizing antibodies to protein therapeutics

2011 ◽  
Vol 54 (2) ◽  
pp. 351-358 ◽  
Author(s):  
Deborah Finco ◽  
Daniel Baltrukonis ◽  
Adrienne Clements-Egan ◽  
Kathy Delaria ◽  
George R. Gunn ◽  
...  
Keyword(s):  
Ligand Binding ◽  
Neutralizing Antibodies ◽  
Binding Assay ◽  
Protein Therapeutics ◽  
Ligand Binding Assay ◽  
Competitive Ligand

A competitive ligand-binding assay to detect neutralizing antibodies to a bispecific drug using a used multiplex Meso Scale Discovery platform

Bioanalysis ◽  
2021 ◽  
Author(s):  
Vitaly Ablamunits ◽  
Soma Basak ◽  
Rosemary Lawrence-Henderson ◽  
Teresa M Caiazzo ◽  
John Kamerud
Keyword(s):  
Ligand Binding ◽  
Neutralizing Antibodies ◽  
Binding Assay ◽  
Large Molecule ◽  
Ligand Binding Assay ◽  
Meso Scale Discovery ◽  
Candidate Drug ◽  
Meso Scale ◽  
Competitive Ligand ◽  
Better Than

Background: Monitoring appearance of neutralizing antibodies (NAbs) to multidomain large molecule drugs is a challenging task. Materials & methods: Here, we report development of a competitive ligand-binding assay for detection of NAbs to a bispecific candidate drug using a used multiplex Meso Scale Discovery platform, which allows for detection of NAbs to both drug arms in the same sample. Results: The assay has sensitivity better than 250 ng/ml and is tolerant to the presence of drug at concentration >600 μg/ml and to the level of soluble target(s) >400 ng/ml. Conclusion: Our data suggest that multiplex approach can be successfully used for development of NAb assays in competitive ligand-binding assay format.

TBG MEASUREMENTS BY COMPETITIVE LIGAND BINDING ASSAY (CLBA)

1975 ◽  
Vol 80 (1_Suppla) ◽  
pp. S15
Author(s):  
K. H. Rudorff ◽  
H. J. Kröll ◽  
J. Herrmann
Keyword(s):  
Ligand Binding ◽  
Binding Assay ◽  
Ligand Binding Assay ◽  
Competitive Ligand

SERUM THYROXINE-BINDING GLOBULIN: DETERMINATION BY COMPETITIVE LIGAND-BINDING ASSAY IN THYROID DISEASE AND PREGNANCY

1977 ◽  
Vol 85 (2) ◽  
pp. 314-324 ◽  
Author(s):  
C. Mulaisho ◽  
R. D. Utiger
Keyword(s):  
Ligand Binding ◽  
Pregnant Women ◽  
Binding Assay ◽  
Normal Subjects ◽  
First Trimester ◽  
Ligand Binding Assay ◽  
Hormone Production ◽  
Thyroxine Binding Globulin ◽  
Serum Thyroxine ◽  
Competitive Ligand

ABSTRACT Serum thyroxine-binding globulin (TBG) concentrations were measured by competitive ligand-binding assay in normal subjects and patients with a variety of abnormalities of thyroid hormone production or TBG production. The mean serum TBG concentration in 73 normal adults was 3.4 ± 0.6 mg/100 ml. No correlations with age, sex or serum thyroxine (T4) or triiodothyronine (T3) concentrations were found. Serum TBG concentrations were normal in patients with hyperthyroidism. They were significantly elevated in hypothyroid patients, and fell to normal with thyroxine treatment. In pregnant women, serum TBG concentrations were markedly increased, being 7.1 ± 1.2 (mean ± sd) mg/100 ml in women in their first trimester, 9.0 ± 1.0 mg/100 ml in the second trimester and 8.9 ± 1.6 mg/100 ml in the third trimester. There was a positive correlation between serum TBG concentration and both serum T4 and serum T3 concentrations in pregnant women. Competitive ligand-binding assay is a simple and reliable method for TBG assay and yields results similar to those of electrophoretic saturation techniques.

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