Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
2480976 | European Journal of Pharmaceutical Sciences | 2011 | 7 Pages |
Abstract
Immunogenicity is a continuous efficacy and safety issue of biopharmaceuticals. Pre-clinical models for prediction of immunogenicity itself as well as biomarkers to reveal potential mechanisms behind an already existing antibody response are still needed. A sensitive, robust and specific immunogenicity assay has therefore been developed that can detect and measure antibodies of five classes against an administered recombinant human protein drug. Additionally, a validation was performed to evaluate the reproducibility and specificity of this newly developed assay. The production of drug-induced antibodies in mice injected with a recombinant human protein drug has been measured by using a modified version of a multi-parametric bead analysis technique. Competitive binding was used to verify drug-specificity of the antibodies. Results showed that the mouse response against the recombinant human protein was IgG1- and IgG2b-specific, suggesting that the drug-induced response was driven by both Th1/Th2 cells; a finding confirmed by measurement of the cytokine profile. With this assay, anti-drug antibody class and subclass screening may be executed in one step.
Keywords
FDAPBSHABAEMEAAPCBSAbovine serum albuminantibodiesAntigen presenting cellsenzyme linked immunosorbent assayEuropean Medicines agencystandard deviationImmunogenicityimmunoglobulin biopharmaceuticalsELISARoom temperatureCV%Food and Drug AdministrationFluorescence intensityconfidence intervalphycoerythrinPhosphate buffered salineLuminexMHCmajor histocompatibility complexquality control
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Authors
Britta Granath, Jan Holgersson, Nina Brenden,