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

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

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

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

^*Corresponding author af dette arbejde

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.

Originalsprog	Engelsk
Tidsskrift	In Vivo
Vol/bind	30
Udgave nummer	5
Sider (fra-til)	557-565
Antal sider	9
ISSN	0258-851X
Status	Udgivet - sep. 2016

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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 (TNF) 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.",

keywords = "Immunogenicity, Infliximab, Therapeutic monoclonal antibodies",

author = "Henriksen, {Maiken Lumby} and Ane Teisner and Jens Kjeldsen and Otto Kalliokoski and Jann Hau and Hansen, {Soren Werner Karlskov}",

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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 - Teisner, Ane

AU - Kjeldsen, Jens

AU - Kalliokoski, Otto

AU - Hau, Jann

AU - Hansen, Soren Werner Karlskov

PY - 2016/9

Y1 - 2016/9

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 (TNF) 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 (TNF) 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 - Immunogenicity

KW - Infliximab

KW - Therapeutic monoclonal antibodies

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M3 - Journal article

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VL - 30

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EP - 565

JO - In Vivo

JF - In Vivo

IS - 5

ER -

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

Abstract

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