Sensitive assay design for detection of anti-drug antibodies to biotherapeutics that lack an immunoglobulin Fc domain

Abstract Today the evaluation of unwanted immunogenicity is a key component in the clinical safety evaluation of new biotherapeutic drugs and macromolecular delivery strategies. However, the evolving structural complexity in contemporary biotherapeutics creates a need for on-going innovation in assa...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Derrick Johnson, Erica Simmons, Sanofar Abdeen, Adam Kinne, Elijah Parmer, Sherri Rinker, Jennifer Thystrup, Swarna Ramaswamy, Ronald R. Bowsher
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/96c6f914c2334dada702d38fc68654fe
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:96c6f914c2334dada702d38fc68654fe
record_format	dspace
spelling	oai:doaj.org-article:96c6f914c2334dada702d38fc68654fe2021-12-02T18:47:08ZSensitive assay design for detection of anti-drug antibodies to biotherapeutics that lack an immunoglobulin Fc domain10.1038/s41598-021-95055-x2045-2322https://doaj.org/article/96c6f914c2334dada702d38fc68654fe2021-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-95055-xhttps://doaj.org/toc/2045-2322Abstract Today the evaluation of unwanted immunogenicity is a key component in the clinical safety evaluation of new biotherapeutic drugs and macromolecular delivery strategies. However, the evolving structural complexity in contemporary biotherapeutics creates a need for on-going innovation in assay designs for reliable detection of anti-drug antibodies, especially for biotherapeutics that may not be well-suited for testing by a bridging assay. We, therefore, initiated systematic optimization of the direct binding assay to adapt it for routine use in regulatory-compliant assays of serum anti-drug antibodies. Accordingly, we first prepared a SULFO-TAG labeled conjugate of recombinant Protein-A/G to create a sensitive electrochemiluminescent secondary detection reagent with broad reactivity to antibodies across many species. Secondly, we evaluated candidate blocker-diluents to identify ones producing the highest signal-to-noise response ratios. Lastly, we introduced use of the ratio of signal responses in biotherapeutic-coated and uncoated wells as a data transformation strategy to identify biological outliers. This alternative data normalization approach improved normality, reduced skewness, and facilitated application of a parametric screening cut point. We believe the optimized direct binding assay design employing SULFO-TAG labeled Protein-A/G represents a useful analytical design for detecting serum ADA to biotherapeutics that lack an immunoglobulin Fc domain.Derrick JohnsonErica SimmonsSanofar AbdeenAdam KinneElijah ParmerSherri RinkerJennifer ThystrupSwarna RamaswamyRonald R. BowsherNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Derrick Johnson Erica Simmons Sanofar Abdeen Adam Kinne Elijah Parmer Sherri Rinker Jennifer Thystrup Swarna Ramaswamy Ronald R. Bowsher Sensitive assay design for detection of anti-drug antibodies to biotherapeutics that lack an immunoglobulin Fc domain
description	Abstract Today the evaluation of unwanted immunogenicity is a key component in the clinical safety evaluation of new biotherapeutic drugs and macromolecular delivery strategies. However, the evolving structural complexity in contemporary biotherapeutics creates a need for on-going innovation in assay designs for reliable detection of anti-drug antibodies, especially for biotherapeutics that may not be well-suited for testing by a bridging assay. We, therefore, initiated systematic optimization of the direct binding assay to adapt it for routine use in regulatory-compliant assays of serum anti-drug antibodies. Accordingly, we first prepared a SULFO-TAG labeled conjugate of recombinant Protein-A/G to create a sensitive electrochemiluminescent secondary detection reagent with broad reactivity to antibodies across many species. Secondly, we evaluated candidate blocker-diluents to identify ones producing the highest signal-to-noise response ratios. Lastly, we introduced use of the ratio of signal responses in biotherapeutic-coated and uncoated wells as a data transformation strategy to identify biological outliers. This alternative data normalization approach improved normality, reduced skewness, and facilitated application of a parametric screening cut point. We believe the optimized direct binding assay design employing SULFO-TAG labeled Protein-A/G represents a useful analytical design for detecting serum ADA to biotherapeutics that lack an immunoglobulin Fc domain.
format	article
author	Derrick Johnson Erica Simmons Sanofar Abdeen Adam Kinne Elijah Parmer Sherri Rinker Jennifer Thystrup Swarna Ramaswamy Ronald R. Bowsher
author_facet	Derrick Johnson Erica Simmons Sanofar Abdeen Adam Kinne Elijah Parmer Sherri Rinker Jennifer Thystrup Swarna Ramaswamy Ronald R. Bowsher
author_sort	Derrick Johnson
title	Sensitive assay design for detection of anti-drug antibodies to biotherapeutics that lack an immunoglobulin Fc domain
title_short	Sensitive assay design for detection of anti-drug antibodies to biotherapeutics that lack an immunoglobulin Fc domain
title_full	Sensitive assay design for detection of anti-drug antibodies to biotherapeutics that lack an immunoglobulin Fc domain
title_fullStr	Sensitive assay design for detection of anti-drug antibodies to biotherapeutics that lack an immunoglobulin Fc domain
title_full_unstemmed	Sensitive assay design for detection of anti-drug antibodies to biotherapeutics that lack an immunoglobulin Fc domain
title_sort	sensitive assay design for detection of anti-drug antibodies to biotherapeutics that lack an immunoglobulin fc domain
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/96c6f914c2334dada702d38fc68654fe
work_keys_str_mv	AT derrickjohnson sensitiveassaydesignfordetectionofantidrugantibodiestobiotherapeuticsthatlackanimmunoglobulinfcdomain AT ericasimmons sensitiveassaydesignfordetectionofantidrugantibodiestobiotherapeuticsthatlackanimmunoglobulinfcdomain AT sanofarabdeen sensitiveassaydesignfordetectionofantidrugantibodiestobiotherapeuticsthatlackanimmunoglobulinfcdomain AT adamkinne sensitiveassaydesignfordetectionofantidrugantibodiestobiotherapeuticsthatlackanimmunoglobulinfcdomain AT elijahparmer sensitiveassaydesignfordetectionofantidrugantibodiestobiotherapeuticsthatlackanimmunoglobulinfcdomain AT sherririnker sensitiveassaydesignfordetectionofantidrugantibodiestobiotherapeuticsthatlackanimmunoglobulinfcdomain AT jenniferthystrup sensitiveassaydesignfordetectionofantidrugantibodiestobiotherapeuticsthatlackanimmunoglobulinfcdomain AT swarnaramaswamy sensitiveassaydesignfordetectionofantidrugantibodiestobiotherapeuticsthatlackanimmunoglobulinfcdomain AT ronaldrbowsher sensitiveassaydesignfordetectionofantidrugantibodiestobiotherapeuticsthatlackanimmunoglobulinfcdomain
_version_	1718377693337092096

Sensitive assay design for detection of anti-drug antibodies to biotherapeutics that lack an immunoglobulin Fc domain

Ejemplares similares