The Effect of Induced Antibodies with Respect to Neutralization, Clearance Rate and Functional Activity in a Rabbit/Infliximab Model
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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; Teisner, Ane; Kjeldsen, Jens; Kalliokoski, Otto; Hau, Jann; Hansen, Soren Werner Karlskov.
In: In Vivo, Vol. 30, No. 5, 09.2016, p. 557-565.Research output: Contribution to journal › Journal article › Research › peer-review
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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 - 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
UR - http://www.scopus.com/inward/record.url?scp=84992084016&partnerID=8YFLogxK
M3 - Journal article
AN - SCOPUS:84992084016
VL - 30
SP - 557
EP - 565
JO - In Vivo
JF - In Vivo
SN - 0258-851X
IS - 5
ER -
ID: 168264277