Progress on the development of human in vitro dendritic cell based assays for assessment of the sensitizing potential of a compound

• Published in: Toxicology and applied pharmacology Vol. 236; no. 3; pp. 372 - 382
• Main Authors: dos Santos, G. Galvão, Reinders, J., Ouwehand, K., Rustemeyer, T., Scheper, R.J., Gibbs, S.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Inc 01.05.2009; Elsevier
• Subjects: 60 APPLIED LIFE SCIENCES; Allergen; ALLERGY; Animal alternative; Animal Testing Alternatives; Animals; Biological and medical sciences; BIOLOGICAL MARKERS; Biomarker; Biomarkers - metabolism; CD34+ derived dendritic cell; CONSUMER PRODUCTS; DENDRITES; Dendritic Cells - cytology; Dendritic Cells - drug effects; DERMATITIS; EU Directive 76/768/EEC; Hematologic and hematopoietic diseases; HUMAN POPULATIONS; Humans; IN VITRO; In Vitro Techniques; Irritant; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; LYMPH NODES; LYMPHOKINES; Medical sciences; Models, Animal; Monocyte derived dendritic cell; MONOCYTES; MUTZ-3; Non-sensitizer; PHOSPHOTRANSFERASES; SENSITIVITY; Sensitizer; SENSITIZERS; SKIN; Test; THP-1; Toxicology; U-937; Validation; Europe; Validation; THP-1; Biomarker; CD34+ derived dendritic cell; U-937; Research; EU Directive 76/768/EEC; MUTZ-3; Irritant; Monocyte derived dendritic cell; Test; Non-sensitizer; Animal alternative; Sensitizer; Allergen; Allergy; Histiocytic lymphoma; Stem cell; Hematopoietic cell; Biological marker; Compounds; Antigen presenting cell; Lymphoproliferative syndrome; Established cell line; Development; Irritation; Human; Immunopathology; Dendritic cell; Monocyte; Malignant hemopathy; Non Hodgkin lymphoma; In vitro; Cell subpopulation; Cell line; Animal; Cancer
• ISSN: 0041-008X; 1096-0333
• DOI: 10.1016/j.taap.2009.02.004

Allergic contact dermatitis is the result of an adaptive immune response of the skin to direct exposure to an allergen. Since many chemicals are also allergens, European regulations require strict screening of all ingredients in consumer products. Until recently, identifying a potential allergen has completely relied on animal testing (e.g.: Local Lymph Node Assay). In addition to the ethical problems, both the 7th Amendment to the Cosmetics Directive and REACH have stimulated the development of alternative tests for the assessment of potential sensitizers. This review is aimed at summarising the progress on cell based assays, in particular dendritic cell based assays, being developed as animal alternatives. Primary cells (CD34 + derived dendritic cells, monocyte derived dendritic cells) as well as dendritic cell-like cell lines (THP-1, U-937, MUTZ-3, KG-1, HL-60, and K562) are extensively described along with biomarkers such as cell surface markers, cytokines, chemokines and kinases. From this review, it can be concluded that no single cell based assay nor single marker is yet able to distinguish all sensitizers from non-sensitizers in a test panel of chemicals, nor is it possible to rank the sensitizing potential of the test chemicals. This suggests that sensitivity and specificity may be increased by a tiered assay approach. Only a limited number of genomic and proteomic studies have been completed until now. Such studies have the potential to identify novel biomarkers for inclusion in future assay development. Although progress is promising, this review suggests that it may be difficult to meet the up and coming European regulatory deadlines.