a novel in vitro assay based on a genomic biomarker signature
Henrik Johansson, Andy Forreryd, Robin Gradin, Angelica Johansson, Olivia Larne, Emil Aaltonen, Anders Jerre, Carl A.K. Borrebaeck and Malin Lindstedt
SenzaGen AB, Lund, Sweden. Department of Immunotechnology, Lund, Sweden.
Exposure to chemicals may induce allergic hypersensitivity reactions in skin or respiratory tract. To minimize exposure, chemicals are routinely screened for their sensitizing potential. Proactive identification has historically been performed using animal models, but the use of animals for safety assessment of cosmetics was recently banned within EU. Today, similar trends are spreading both globally and across industry and market segments. Methods for specific identification of respiratory sensitizers are greatly underdeveloped, with no validated, or even widely used assay readily available. Thus, there is an urgent need for development of non-animal based methods for hazard classification of respiratory sensitizing chemicals.
GARD – Genomic Allergen Rapid Detection – is a state of the art technology platform for assessment of chemical sensitizers (Figure 1). It is based on a dendritic cell (DC)-like cell line, thus mimicking the cell type involved in the initiation of the response leading to sensitization. Following test chemical exposure, induced transcriptional changes are measured to study the activation state of the cells. These changes are associated with the immunological decision-making role of DCs in vivo and constitutes of e.g. up-regulation of co-stimulatory molecules, induction of cellular and oxidative stress pathways and an altered phenotype associated with recognition of xenobiotic matter. By using state-of-the-art gene expression technologies, high informational content data is generated, that allows the user to get a holistic view of the cellular response induced by the test substance.
GARDair is a novel assay for assessment of respiratory sensitizers. It is an adaptation of the GARD platform, utilizing gene expression analysis of predictive biomarker signatures and state-of-the-art data analysis methodology. GARDair has been proven functional and is currently progressing towards industrial implemetation with financial support from the EU programme Horizon 2020. This progress will include scientific verification of results, assay optimization, transfer and formal validation.