A deimmunized and pharmacologically optimized Toll-like receptor 5 agonist for therapeutic applications

Mett et al. describe development of GP532, a substantially deimmunized derivative of Toll-like receptor 5 (TLR5) agonist entolimod. GP532 has mutations eliminating key B- and T-cell epitopes and an inflammasome-activating domain yet remains a potent NF-κB activator with biological effects similar to...

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Main Authors:	Vadim Mett, Oleg V. Kurnasov, Ivan A. Bespalov, Ivan Molodtsov, Craig M. Brackett, Lyudmila G. Burdelya, Andrei A. Purmal, Anatoli S. Gleiberman, Ilia A. Toshkov, Catherine A. Burkhart, Yakov N. Kogan, Ekaterina L. Andrianova, Andrei V. Gudkov, Andrei L. Osterman
Format:	Article
Language:	English
Published:	Nature Publishing Group 2021-04-01
Series:	Communications Biology
Online Access:	https://doi.org/10.1038/s42003-021-01978-6

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spelling	doaj-bcafc6dab7b74c02bc2aec45e9ac993a2021-04-18T11:29:47ZengNature Publishing GroupCommunications Biology2399-36422021-04-014111410.1038/s42003-021-01978-6A deimmunized and pharmacologically optimized Toll-like receptor 5 agonist for therapeutic applicationsVadim Mett0Oleg V. Kurnasov1Ivan A. Bespalov2Ivan Molodtsov3Craig M. Brackett4Lyudmila G. Burdelya5Andrei A. Purmal6Anatoli S. Gleiberman7Ilia A. Toshkov8Catherine A. Burkhart9Yakov N. Kogan10Ekaterina L. Andrianova11Andrei V. Gudkov12Andrei L. Osterman13Buffalo BioLabs, LLCSanford Burnham Prebys Medical Discovery InstituteGenome Protection, Inc.Gamaleya Research Center of Epidemiology and MicrobiologyRoswell Park Comprehensive Cancer CenterRoswell Park Comprehensive Cancer CenterGenome Protection, Inc.Genome Protection, Inc.Genome Protection, Inc.Buffalo BioLabs, LLCGenome Protection, Inc.Genome Protection, Inc.Genome Protection, Inc.Sanford Burnham Prebys Medical Discovery InstituteMett et al. describe development of GP532, a substantially deimmunized derivative of Toll-like receptor 5 (TLR5) agonist entolimod. GP532 has mutations eliminating key B- and T-cell epitopes and an inflammasome-activating domain yet remains a potent NF-κB activator with biological effects similar to entolimod. Thus, GP532 is suitable for multi-dose TLR5-targeting therapies and patients with high titers of preexisting flagellin-neutralizing antibodies.https://doi.org/10.1038/s42003-021-01978-6
collection	DOAJ
language	English
format	Article
sources	DOAJ
author	Vadim Mett Oleg V. Kurnasov Ivan A. Bespalov Ivan Molodtsov Craig M. Brackett Lyudmila G. Burdelya Andrei A. Purmal Anatoli S. Gleiberman Ilia A. Toshkov Catherine A. Burkhart Yakov N. Kogan Ekaterina L. Andrianova Andrei V. Gudkov Andrei L. Osterman
spellingShingle	Vadim Mett Oleg V. Kurnasov Ivan A. Bespalov Ivan Molodtsov Craig M. Brackett Lyudmila G. Burdelya Andrei A. Purmal Anatoli S. Gleiberman Ilia A. Toshkov Catherine A. Burkhart Yakov N. Kogan Ekaterina L. Andrianova Andrei V. Gudkov Andrei L. Osterman A deimmunized and pharmacologically optimized Toll-like receptor 5 agonist for therapeutic applications Communications Biology
author_facet	Vadim Mett Oleg V. Kurnasov Ivan A. Bespalov Ivan Molodtsov Craig M. Brackett Lyudmila G. Burdelya Andrei A. Purmal Anatoli S. Gleiberman Ilia A. Toshkov Catherine A. Burkhart Yakov N. Kogan Ekaterina L. Andrianova Andrei V. Gudkov Andrei L. Osterman
author_sort	Vadim Mett
title	A deimmunized and pharmacologically optimized Toll-like receptor 5 agonist for therapeutic applications
title_short	A deimmunized and pharmacologically optimized Toll-like receptor 5 agonist for therapeutic applications
title_full	A deimmunized and pharmacologically optimized Toll-like receptor 5 agonist for therapeutic applications
title_fullStr	A deimmunized and pharmacologically optimized Toll-like receptor 5 agonist for therapeutic applications
title_full_unstemmed	A deimmunized and pharmacologically optimized Toll-like receptor 5 agonist for therapeutic applications
title_sort	deimmunized and pharmacologically optimized toll-like receptor 5 agonist for therapeutic applications
publisher	Nature Publishing Group
series	Communications Biology
issn	2399-3642
publishDate	2021-04-01
description	Mett et al. describe development of GP532, a substantially deimmunized derivative of Toll-like receptor 5 (TLR5) agonist entolimod. GP532 has mutations eliminating key B- and T-cell epitopes and an inflammasome-activating domain yet remains a potent NF-κB activator with biological effects similar to entolimod. Thus, GP532 is suitable for multi-dose TLR5-targeting therapies and patients with high titers of preexisting flagellin-neutralizing antibodies.
url	https://doi.org/10.1038/s42003-021-01978-6
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A deimmunized and pharmacologically optimized Toll-like receptor 5 agonist for therapeutic applications

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