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The trimer to monomer transition of Tumor Necrosis Factor-Alpha is a dynamic process that is significantly altered by therapeutic antibodies

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The trimer to monomer transition of Tumor Necrosis Factor-Alpha is a dynamic process that is significantly altered by therapeutic antibodies. / Daub, Herwin; Traxler, Lukas; Ismajli, Fjolla; Groitl, Bastian; Itzen, Aymelt; Rant, Ulrich.

in: SCI REP-UK, Jahrgang 10, Nr. 1, 09.06.2020, S. 9265.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Daub, H, Traxler, L, Ismajli, F, Groitl, B, Itzen, A & Rant, U 2020, 'The trimer to monomer transition of Tumor Necrosis Factor-Alpha is a dynamic process that is significantly altered by therapeutic antibodies', SCI REP-UK, Jg. 10, Nr. 1, S. 9265. https://doi.org/10.1038/s41598-020-66123-5

APA

Daub, H., Traxler, L., Ismajli, F., Groitl, B., Itzen, A., & Rant, U. (2020). The trimer to monomer transition of Tumor Necrosis Factor-Alpha is a dynamic process that is significantly altered by therapeutic antibodies. SCI REP-UK, 10(1), 9265. https://doi.org/10.1038/s41598-020-66123-5

Vancouver

Daub H, Traxler L, Ismajli F, Groitl B, Itzen A, Rant U. The trimer to monomer transition of Tumor Necrosis Factor-Alpha is a dynamic process that is significantly altered by therapeutic antibodies. SCI REP-UK. 2020 Jun 9;10(1):9265. https://doi.org/10.1038/s41598-020-66123-5

Bibtex

@article{80a67e996fc642f297f92b309aef368e,
title = "The trimer to monomer transition of Tumor Necrosis Factor-Alpha is a dynamic process that is significantly altered by therapeutic antibodies",
abstract = "The cytokine tumor necrosis factor-alpha (TNF-α) readily forms homotrimers at sub-nM concentrations to promote inflammation. For the treatment of inflammatory diseases with upregulated levels of TNF-α, a number of therapeutic antibodies are currently used as scavengers to reduce the active TNF-α concentration in patients. Despite their clinical success, the mode-of-action of different antibody formats with regard to a stabilization of the trimeric state is not entirely understood. Here, we use a biosensor with dynamic nanolevers to analyze the monomeric and trimeric states of TNF-α together with the binding kinetics of therapeutic biologics. The intrinsic trimer-to-monomer decay rate k = 1.7 × 10-3 s-1 could be measured directly using a microfluidic system, and antibody binding affinities were analyzed in the pM range. Trimer stabilization effects are quantified for Adalimumab, Infliximab, Etanercept, Certolizumab, Golimumab for bivalent and monovalent binding formats. Clear differences in trimer stabilization are observed, which may provide a deeper insight into the mode-of-action of TNF-α scavengers.",
author = "Herwin Daub and Lukas Traxler and Fjolla Ismajli and Bastian Groitl and Aymelt Itzen and Ulrich Rant",
year = "2020",
month = jun,
day = "9",
doi = "10.1038/s41598-020-66123-5",
language = "English",
volume = "10",
pages = "9265",
journal = "SCI REP-UK",
issn = "2045-2322",
publisher = "NATURE PUBLISHING GROUP",
number = "1",

}

RIS

TY - JOUR

T1 - The trimer to monomer transition of Tumor Necrosis Factor-Alpha is a dynamic process that is significantly altered by therapeutic antibodies

AU - Daub, Herwin

AU - Traxler, Lukas

AU - Ismajli, Fjolla

AU - Groitl, Bastian

AU - Itzen, Aymelt

AU - Rant, Ulrich

PY - 2020/6/9

Y1 - 2020/6/9

N2 - The cytokine tumor necrosis factor-alpha (TNF-α) readily forms homotrimers at sub-nM concentrations to promote inflammation. For the treatment of inflammatory diseases with upregulated levels of TNF-α, a number of therapeutic antibodies are currently used as scavengers to reduce the active TNF-α concentration in patients. Despite their clinical success, the mode-of-action of different antibody formats with regard to a stabilization of the trimeric state is not entirely understood. Here, we use a biosensor with dynamic nanolevers to analyze the monomeric and trimeric states of TNF-α together with the binding kinetics of therapeutic biologics. The intrinsic trimer-to-monomer decay rate k = 1.7 × 10-3 s-1 could be measured directly using a microfluidic system, and antibody binding affinities were analyzed in the pM range. Trimer stabilization effects are quantified for Adalimumab, Infliximab, Etanercept, Certolizumab, Golimumab for bivalent and monovalent binding formats. Clear differences in trimer stabilization are observed, which may provide a deeper insight into the mode-of-action of TNF-α scavengers.

AB - The cytokine tumor necrosis factor-alpha (TNF-α) readily forms homotrimers at sub-nM concentrations to promote inflammation. For the treatment of inflammatory diseases with upregulated levels of TNF-α, a number of therapeutic antibodies are currently used as scavengers to reduce the active TNF-α concentration in patients. Despite their clinical success, the mode-of-action of different antibody formats with regard to a stabilization of the trimeric state is not entirely understood. Here, we use a biosensor with dynamic nanolevers to analyze the monomeric and trimeric states of TNF-α together with the binding kinetics of therapeutic biologics. The intrinsic trimer-to-monomer decay rate k = 1.7 × 10-3 s-1 could be measured directly using a microfluidic system, and antibody binding affinities were analyzed in the pM range. Trimer stabilization effects are quantified for Adalimumab, Infliximab, Etanercept, Certolizumab, Golimumab for bivalent and monovalent binding formats. Clear differences in trimer stabilization are observed, which may provide a deeper insight into the mode-of-action of TNF-α scavengers.

U2 - 10.1038/s41598-020-66123-5

DO - 10.1038/s41598-020-66123-5

M3 - SCORING: Journal article

C2 - 32518229

VL - 10

SP - 9265

JO - SCI REP-UK

JF - SCI REP-UK

SN - 2045-2322

IS - 1

ER -