A universal reporter cell line for bioactivity evaluation of engineered cytokine products

Abstract Engineered cytokine products represent a growing class of therapeutic proteins which need to be tested for biological activity at various stages of pharmaceutical development. In most cases, dedicated biological assays are established for different products, in a process that can be time-co...

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Autores principales:	Jacqueline Mock, Christian Pellegrino, Dario Neri
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/24f36847b7134e45b1c03f29bc469dc3
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spelling	oai:doaj.org-article:24f36847b7134e45b1c03f29bc469dc32021-12-02T14:28:22ZA universal reporter cell line for bioactivity evaluation of engineered cytokine products10.1038/s41598-020-60182-42045-2322https://doaj.org/article/24f36847b7134e45b1c03f29bc469dc32020-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-60182-4https://doaj.org/toc/2045-2322Abstract Engineered cytokine products represent a growing class of therapeutic proteins which need to be tested for biological activity at various stages of pharmaceutical development. In most cases, dedicated biological assays are established for different products, in a process that can be time-consuming and cumbersome. Here we describe the development and implementation of a universal cell-based reporter system for various classes of immunomodulatory proteins. The novel system capitalizes on the fact that the signaling of various types of pro-inflammatory agents (e.g., cytokines, chemokines, Toll-like receptor agonists) may involve transcriptional activation by NF-κB. Using viral transduction, we generated stably-transformed cell lines of B or T lymphocyte origin and compared the new reporter cell lines with conventional bioassays. The experimental findings with various interleukins and with members of the TNF superfamily revealed that the newly-developed “universal” bioassay method yielded bioactivity data which were comparable to the ones obtained with dedicated conventional methods. The engineered cell lines with reporters for NF-κB were tested with several antibody-cytokine fusions and may be generally useful for the characterization of novel immunomodulatory products. The newly developed methodology also revealed a mechanism for cytokine potentiation, based on the antibody-mediated clustering of TNF superfamily members on tumor-associated extracellular matrix components.Jacqueline MockChristian PellegrinoDario NeriNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-10 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jacqueline Mock Christian Pellegrino Dario Neri A universal reporter cell line for bioactivity evaluation of engineered cytokine products
description	Abstract Engineered cytokine products represent a growing class of therapeutic proteins which need to be tested for biological activity at various stages of pharmaceutical development. In most cases, dedicated biological assays are established for different products, in a process that can be time-consuming and cumbersome. Here we describe the development and implementation of a universal cell-based reporter system for various classes of immunomodulatory proteins. The novel system capitalizes on the fact that the signaling of various types of pro-inflammatory agents (e.g., cytokines, chemokines, Toll-like receptor agonists) may involve transcriptional activation by NF-κB. Using viral transduction, we generated stably-transformed cell lines of B or T lymphocyte origin and compared the new reporter cell lines with conventional bioassays. The experimental findings with various interleukins and with members of the TNF superfamily revealed that the newly-developed “universal” bioassay method yielded bioactivity data which were comparable to the ones obtained with dedicated conventional methods. The engineered cell lines with reporters for NF-κB were tested with several antibody-cytokine fusions and may be generally useful for the characterization of novel immunomodulatory products. The newly developed methodology also revealed a mechanism for cytokine potentiation, based on the antibody-mediated clustering of TNF superfamily members on tumor-associated extracellular matrix components.
format	article
author	Jacqueline Mock Christian Pellegrino Dario Neri
author_facet	Jacqueline Mock Christian Pellegrino Dario Neri
author_sort	Jacqueline Mock
title	A universal reporter cell line for bioactivity evaluation of engineered cytokine products
title_short	A universal reporter cell line for bioactivity evaluation of engineered cytokine products
title_full	A universal reporter cell line for bioactivity evaluation of engineered cytokine products
title_fullStr	A universal reporter cell line for bioactivity evaluation of engineered cytokine products
title_full_unstemmed	A universal reporter cell line for bioactivity evaluation of engineered cytokine products
title_sort	universal reporter cell line for bioactivity evaluation of engineered cytokine products
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/24f36847b7134e45b1c03f29bc469dc3
work_keys_str_mv	AT jacquelinemock auniversalreportercelllineforbioactivityevaluationofengineeredcytokineproducts AT christianpellegrino auniversalreportercelllineforbioactivityevaluationofengineeredcytokineproducts AT darioneri auniversalreportercelllineforbioactivityevaluationofengineeredcytokineproducts AT jacquelinemock universalreportercelllineforbioactivityevaluationofengineeredcytokineproducts AT christianpellegrino universalreportercelllineforbioactivityevaluationofengineeredcytokineproducts AT darioneri universalreportercelllineforbioactivityevaluationofengineeredcytokineproducts
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A universal reporter cell line for bioactivity evaluation of engineered cytokine products

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