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

• Published in: Methods in molecular biology (Clifton, N.J.) Vol. 598; p. 27
• Main Authors: Ludwig, Irene S, Kwast, Lydia M, Fiechter, Daniëlle, Pieters, Raymond H H
• Format: Journal Article
• Language: English
• Published: United States 2010
• Subjects: Animals; Antigens - immunology; Cell Culture Techniques; Enzyme-Linked Immunosorbent Assay - methods; Female; Humans; Hypersensitivity, Delayed - immunology; Immunization - methods; Lymph Nodes - cytology; Lymph Nodes - immunology; Mice; Molecular Weight; Random Allocation; T-Lymphocytes - cytology; T-Lymphocytes - immunology
• ISSN: 1940-6029
• DOI: 10.1007/978-1-60761-401-2_3

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.