An in vivo tiered approach to test immunosensitization by low molecular weight compounds.

Published on Jan 1, 2010in Methods of Molecular Biology
· DOI :10.1007/978-1-60761-401-2_3
Irene S. Ludwig12
Estimated H-index: 12
(UU: Utrecht University),
Lydia M. Kwast5
Estimated H-index: 5
(UU: Utrecht University)
+ 1 AuthorsRaymond Pieters36
Estimated H-index: 36
(UU: Utrecht University)
: New chemical entities are tested in general toxicity assays during development before entering clinical trials. However, immunosensitization of these entities is not tested on a standard basis. There are no in vitro or in vivo standardized methods available for testing immunosensitization or immunostimulation. In this chapter, we describe a tiered strategy oral exposure model for assessing immunosensitization or immunostimulation capacity of low molecular weight compounds. The strategy starts from a set of data that may provide information on bioactivation, conjugation (hapten-protein conjugate formation), cytotoxicity and signs of inflammation in any of the animals in a 28 day-toxicity study. In case of concern, a reporter antigen-popliteal lymph node assay (RA-PLNA) and, subsequently, an oral exposure experiment with the reporter antigen can be performed. Based on the presence of RA-specific immune responses an indication for immunosensitization can be found.
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