RT Journal Article
SR Electronic
T1 The Effect of Induced Antibodies with Respect to Neutralization, Clearance Rate and Functional Activity in a Rabbit/Infliximab Model
JF In Vivo
JO In Vivo
FD International Institute of Anticancer Research
SP 557
OP 565
VO 30
IS 5
A1 MAIKEN LUMBY HENRIKSEN
A1 ANE TEISNER
A1 JENS KJELDSEN
A1 OTTO KALLIOKOSKI
A1 JANN HAU
A1 SOREN WERNER KARLSKOV HANSEN
YR 2016
UL http://iv.iiarjournals.org/content/30/5/557.abstract
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.