The Effect of Induced Antibodies with Respect to Neutralization, Clearance Rate and Functional Activity in a Rabbit/Infliximab Model

Maiken Lumby Henriksen, Ane Søgaard Teisner, Jens Kjeldsen, Otto Kalliokoski, Jann Hau, Soren Werner Karlskov Hansen

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

BACKGROUND: Therapeutic antibodies are a developing field for treatment of an expanding number of inflammatory diseases, including Crohn's disease. Treatment with monoclonal antibodies is frequently hampered by development of anti-drug antibodies (ADAs) that may compromise the treatment.

MATERIALS AND METHODS: We addressed this issue in a rabbit model of treatment with the anti-tumor-necrosis factor alpha (TNFα) antibody, infliximab (IFX). We developed an inhibition ELISA to selectively measure absolute concentrations of neutralizing antibodies and another ELISA for measuring the concentration of functional IFX in the circulation.

RESULTS: We found that the concentration of functional IFX was inversely proportional to the concentration of neutralizing antibodies.

CONCLUSION: Administration of IFX to rabbits showed diversity in immune responses/tolerance toward IFX, corresponding to responses observed in patients. The applied assay technology is easily adapted to human plasma samples and/or other therapeutic antibodies, including fully humanized antibodies, for which immunogenicity also is observed.

Original languageEnglish
JournalIn Vivo
Volume30
Issue number5
Pages (from-to)557-565
ISSN0258-851X
Publication statusPublished - 2016

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Rabbits
Antibodies
Neutralizing Antibodies
Plasma (human)
Antibodies, Monoclonal, Humanized
Assays
Crohn Disease
Tumor Necrosis Factor-alpha
Monoclonal Antibodies
Infliximab
Pharmaceutical Preparations

Keywords

  • Journal Article

Cite this

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title = "The Effect of Induced Antibodies with Respect to Neutralization, Clearance Rate and Functional Activity in a Rabbit/Infliximab Model",
abstract = "BACKGROUND: Therapeutic antibodies are a developing field for treatment of an expanding number of inflammatory diseases, including Crohn's disease. Treatment with monoclonal antibodies is frequently hampered by development of anti-drug antibodies (ADAs) that may compromise the treatment.MATERIALS AND METHODS: We addressed this issue in a rabbit model of treatment with the anti-tumor-necrosis factor alpha (TNFα) antibody, infliximab (IFX). We developed an inhibition ELISA to selectively measure absolute concentrations of neutralizing antibodies and another ELISA for measuring the concentration of functional IFX in the circulation.RESULTS: We found that the concentration of functional IFX was inversely proportional to the concentration of neutralizing antibodies.CONCLUSION: Administration of IFX to rabbits showed diversity in immune responses/tolerance toward IFX, corresponding to responses observed in patients. The applied assay technology is easily adapted to human plasma samples and/or other therapeutic antibodies, including fully humanized antibodies, for which immunogenicity also is observed.",
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author = "Henriksen, {Maiken Lumby} and {S{\o}gaard Teisner}, Ane and Jens Kjeldsen and Otto Kalliokoski and Jann Hau and Hansen, {Soren Werner Karlskov}",
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year = "2016",
language = "English",
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The Effect of Induced Antibodies with Respect to Neutralization, Clearance Rate and Functional Activity in a Rabbit/Infliximab Model. / Henriksen, Maiken Lumby; Søgaard Teisner, Ane; Kjeldsen, Jens; Kalliokoski, Otto; Hau, Jann; Hansen, Soren Werner Karlskov.

In: In Vivo, Vol. 30, No. 5, 2016, p. 557-565 .

Research output: Contribution to journalJournal articleResearchpeer-review

TY - JOUR

T1 - The Effect of Induced Antibodies with Respect to Neutralization, Clearance Rate and Functional Activity in a Rabbit/Infliximab Model

AU - Henriksen, Maiken Lumby

AU - Søgaard Teisner, Ane

AU - Kjeldsen, Jens

AU - Kalliokoski, Otto

AU - Hau, Jann

AU - Hansen, Soren Werner Karlskov

N1 - Copyright © 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

PY - 2016

Y1 - 2016

N2 - BACKGROUND: Therapeutic antibodies are a developing field for treatment of an expanding number of inflammatory diseases, including Crohn's disease. Treatment with monoclonal antibodies is frequently hampered by development of anti-drug antibodies (ADAs) that may compromise the treatment.MATERIALS AND METHODS: We addressed this issue in a rabbit model of treatment with the anti-tumor-necrosis factor alpha (TNFα) antibody, infliximab (IFX). We developed an inhibition ELISA to selectively measure absolute concentrations of neutralizing antibodies and another ELISA for measuring the concentration of functional IFX in the circulation.RESULTS: We found that the concentration of functional IFX was inversely proportional to the concentration of neutralizing antibodies.CONCLUSION: Administration of IFX to rabbits showed diversity in immune responses/tolerance toward IFX, corresponding to responses observed in patients. The applied assay technology is easily adapted to human plasma samples and/or other therapeutic antibodies, including fully humanized antibodies, for which immunogenicity also is observed.

AB - BACKGROUND: Therapeutic antibodies are a developing field for treatment of an expanding number of inflammatory diseases, including Crohn's disease. Treatment with monoclonal antibodies is frequently hampered by development of anti-drug antibodies (ADAs) that may compromise the treatment.MATERIALS AND METHODS: We addressed this issue in a rabbit model of treatment with the anti-tumor-necrosis factor alpha (TNFα) antibody, infliximab (IFX). We developed an inhibition ELISA to selectively measure absolute concentrations of neutralizing antibodies and another ELISA for measuring the concentration of functional IFX in the circulation.RESULTS: We found that the concentration of functional IFX was inversely proportional to the concentration of neutralizing antibodies.CONCLUSION: Administration of IFX to rabbits showed diversity in immune responses/tolerance toward IFX, corresponding to responses observed in patients. The applied assay technology is easily adapted to human plasma samples and/or other therapeutic antibodies, including fully humanized antibodies, for which immunogenicity also is observed.

KW - Journal Article

M3 - Journal article

VL - 30

SP - 557

EP - 565

JO - In Vivo

JF - In Vivo

SN - 0258-851X

IS - 5

ER -