Immuno-PCR assays for immunogenicity testing.

Authors:
Mark Spengler
Mark Spengler
Technische Universität Dortmund
Germany
Michael Adler
Michael Adler
Université Libre de Bruxelles
Belgium
Christof M Niemeyer
Christof M Niemeyer
Universität Dortmund
Germany

Biochem Biophys Res Commun 2009 Sep 3;387(2):278-82. Epub 2009 Jul 3.

Chimera Biotec GmbH, D-44227 Dortmund, Germany.

The administration of therapeutic proteins often induces immunogenic response and thus formation of anti-drug antibodies (ADA), which can neutralize the drug's therapeutic effect and may even cause serious health problems. We here report on the employment of the ultra-sensitive immuno-PCR (IPCR) method to facilitate immunogenicity testing using two established assay formats. In a "bridging assay", in which ADA forms a bridge to immobilize a signal-generating drug reporter probe, IPCR detection enabled an at least 1000-fold increase in sensitivity, as compared to the analogous ELISA, along with a high drug tolerance value. Moreover, we demonstrate that interfering effects of the biological matrix can be omitted by a simple dilution of analytical samples without loss in assay performance. In a cell-free "neutralizing assay", in which a labeled drug reporter probe competes for binding to either surface-bound receptors or neutralizing ADA, the IPCR assay also revealed high sensitivity. These results suggest that IPCR has the potential to become a standard methodology in immunogenicity testing.

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Source
http://linkinghub.elsevier.com/retrieve/pii/S0006291X0901324
Publisher Site
http://dx.doi.org/10.1016/j.bbrc.2009.07.001DOI Listing

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September 2009
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