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

Abstract Dostarlimab 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 efficac...

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Autores principales:	Xiaolong Tom Zhang, Hong Chen, Weiping Shao, Zhongping John Lin, Murad Melhem, Sharon Lu
Formato:	article
Lenguaje:	EN
Publicado:	SpringerOpen 2021
Materias:	Dostarlimab Endometrial cancer Neutralizing antibodies Immunotherapy Competitive ligand-binding assay Therapeutics. Pharmacology RM1-950 Pharmacy and materia medica RS1-441
Acceso en línea:	https://doaj.org/article/9cc562b825a24dee8a7fce5d389aa00c
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spelling	oai:doaj.org-article:9cc562b825a24dee8a7fce5d389aa00c2021-11-21T12:15:51ZA competitive ligand-binding assay for the detection of neutralizing antibodies against dostarlimab (TSR-042)10.1186/s41120-021-00039-w2364-9534https://doaj.org/article/9cc562b825a24dee8a7fce5d389aa00c2021-11-01T00:00:00Zhttps://doi.org/10.1186/s41120-021-00039-whttps://doaj.org/toc/2364-9534Abstract Dostarlimab 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 2016Xiaolong Tom ZhangHong ChenWeiping ShaoZhongping John LinMurad MelhemSharon LuSpringerOpenarticleDostarlimabEndometrial cancerNeutralizing antibodiesImmunotherapyCompetitive ligand-binding assayTherapeutics. PharmacologyRM1-950Pharmacy and materia medicaRS1-441ENAAPS Open, Vol 7, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Dostarlimab Endometrial cancer Neutralizing antibodies Immunotherapy Competitive ligand-binding assay Therapeutics. Pharmacology RM1-950 Pharmacy and materia medica RS1-441
spellingShingle	Dostarlimab Endometrial cancer Neutralizing antibodies Immunotherapy Competitive ligand-binding assay Therapeutics. Pharmacology RM1-950 Pharmacy and materia medica RS1-441 Xiaolong Tom Zhang Hong Chen Weiping Shao Zhongping John Lin Murad Melhem Sharon Lu A competitive ligand-binding assay for the detection of neutralizing antibodies against dostarlimab (TSR-042)
description	Abstract Dostarlimab 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
format	article
author	Xiaolong Tom Zhang Hong Chen Weiping Shao Zhongping John Lin Murad Melhem Sharon Lu
author_facet	Xiaolong Tom Zhang Hong Chen Weiping Shao Zhongping John Lin Murad Melhem Sharon Lu
author_sort	Xiaolong Tom Zhang
title	A competitive ligand-binding assay for the detection of neutralizing antibodies against dostarlimab (TSR-042)
title_short	A competitive ligand-binding assay for the detection of neutralizing antibodies against dostarlimab (TSR-042)
title_full	A competitive ligand-binding assay for the detection of neutralizing antibodies against dostarlimab (TSR-042)
title_fullStr	A competitive ligand-binding assay for the detection of neutralizing antibodies against dostarlimab (TSR-042)
title_full_unstemmed	A competitive ligand-binding assay for the detection of neutralizing antibodies against dostarlimab (TSR-042)
title_sort	competitive ligand-binding assay for the detection of neutralizing antibodies against dostarlimab (tsr-042)
publisher	SpringerOpen
publishDate	2021
url	https://doaj.org/article/9cc562b825a24dee8a7fce5d389aa00c
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A competitive ligand-binding assay for the detection of neutralizing antibodies against dostarlimab (TSR-042)

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