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senzagen gard session

SenzaGen is presenting at hosted sessions at Society of Toxicology 56th Annual Meeting in Baltimore March 12-16, 2017

Lund University Scientist Andy Forreryd and SenzaGen CEO Anki Malmborg Hager will give a presentatios about the GARD assay at exhibitor hosted sessions at the Society of Toxicology 56th Annual Meeting in Baltimore, on the 13th and 14th of March.

The meeting promises more than 150 scientific sessions, approximately 350 ToxExpo exhibitors offering you the latest information on services and technology, thousands of abstract presentations, continuing education courses, awards presentations, receptions, career guidance and support, and more.

Presentations details

– Replacement of Animal Testing for CLP/GHS Classification of Skin Sensitizers is now possible using a Modified Genomic GARDskin [OECD TGP 4.106] Assay
SenzaGen presents the latest development towards reliable potency classification of chemicals according to CLP 1A and 1B, taking both LLNA and Human potency data in consideration. The assay is based on GARDskin and utilizes a refined gene expression signature developed specifically for potency categorization with high predictability.

Date: 3/13 Time: 13:30 -14:30  Room: 338

– Advantages with Genome Testing Opening up the Landscape for New Application Possibilities for Sensitization Testing using SenzaGen’s Genomic GARD Assay
SenzaGen’s GARD assay is based on expression analysis of predictive genomic biomarker signatures. Prediction calls of test substances are generated by computational methods based on machine learning. SenzaGen presents their experience in skin and respiratory sensitization testing, working with challenging compounds and mixtures, active substances, potency classification and NOEL interpretation.

Date: 3/14 Time: 13:30-14:30  Room: 338

These session are Exhibitor-Hosted Session. Although not an official part of the SOT Annual Meeting scientific program, its presentation is permitted by the Society.

Attendees are welcomed from researcher community, industry, manufacturers, regulatory agencies, consultants, CROs and every one interested in safety testing of chemical compounds.

Testing Human Skin and Respiratory Sensitizers—What Is Good Enough?

Int. J. Mol. Sci. 2017, 18(2), 241; doi:10.3390/ijms18020241

Malmborg A., Borrebaeck C. A.K.

Abstract

Alternative methods for accurate in vitro assessment of skin and respiratory sensitizers are urgently needed. Sensitization is a complex biological process that cannot be evaluated accurately using single events or biomarkers, since the information content is too restricted in these measurements. On the contrary, if the tremendous information content harbored in DNA/mRNA could be mined, most complex biological processes could be elucidated. Genomic technologies available today, including transcriptional profiling and next generation sequencing, have the power to decipher sensitization, when used in the right context. Thus, a genomic test platform has been developed, denoted the Genomic Allergen Rapid Detection (GARD) assay. Due to the high informational content of the GARD test, accurate predictions of both the skin and respiratory sensitizing capacity of chemicals, have been demonstrated. Based on a matured dendritic cell line, acting as a human-like reporter system, information about potency has also been acquired. Consequently, multiparametric diagnostic technologies are disruptive test principles that can change the way in which the next generation of alternative methods are designed.
Keywords:

genomics; skin sensitization; adverse outcome pathways; next generation in vitro tests

Next generation skin sensitisation testing.

Personal Care Magazine Europe, sept 2016

Malmborg Hager A., Johansson H., Lindstedt M., Borrebaeck CA.

 

DNA is the software that predicts human phenotypes. Genomics utilises DNA as such a piece of software, which in several recent applications has been demonstrated to be able to predict a number of biological features, enabling anything from face recognition to vaccine development. The tremendous information content, harboured in the DNA, should be harnessed in tests of cosmetic ingredients and formulations, to get a complete insight into what is happening in the body when these types of products are applied to the human skin. This type of complex information gives a holistic view of a human condition that many of us are familiar with, such as e.g. allergic contact dermatitis, and has the potential not only to classify chemicals used in cosmetics but also to determine the magnitude to which a
chemical affects the human body (the potency).

This distinguishes genomics from most other test principles, where in many cases only one or two markers are being
monitored, such as DC activation markers (CD86, CD54), genes involved in cytoprotective responses to oxidative stress or electrophilic compounds (Nrf2, Keap1), or proinflammatory cytokines, (e.g. IL18).

Next generation skin sensitisation testing. PC Magazine, Sept 2016. Malmborg Hager A., Johansson H., Lindstedt M., Borrebaeck CA.

From genome-wide arrays to tailor-made biomarker readout – Progress towards routine analysis of skin sensitizing chemicals with GARD.

Toxicol In Vitro. 2016 Dec;37:178-188. doi: 10.1016/j.tiv.2016.09.013. Epub 2016 Sep 13.

Forreryd A., Zeller K., Lindberg T., Johansson H., Lindstedt M

Abstract

Allergic contact dermatitis (ACD) initiated by chemical sensitizers is an important public health concern. To prevent ACD, it is important to identify chemical allergens to limit the use of such compounds in various products. EU legislations, as well as increased mechanistic knowledge of skin sensitization have promoted development of non-animal based approaches for hazard classification of chemicals. GARD is an in vitro testing strategy based on measurements of a genomic biomarker signature. However, current GARD protocols are optimized for identification of predictive biomarker signatures, and not suitable for standardized screening. This study describes improvements to GARD to progress from biomarker discovery into a reliable and cost-effective assay for routine testing. Gene expression measurements were transferred to NanoString nCounter platform, normalization strategy was adjusted to fit serial arrival of testing substances, and a novel strategy to correct batch variations was presented. When challenging GARD with 29 compounds, sensitivity, specificity and accuracy could be estimated to 94%, 83% and 90%, respectively. In conclusion, we present a GARD workflow with improved sample capacity, retained predictive performance, and in a format adapted to standardized screening. We propose that GARD is ready to be considered as part of an integrated testing strategy for skin sensitization.

KEYWORDS:

GARD; In vitro assay; Predictive genomic biomarker signature; Skin sensitization

Link to articel on line

SenzaGen AB, a diagnostic spin-off company from Lund University, reports the launch of a new product for respiratory sensitization testing

SenzaGen AB is a diagnostic company working to replace animal testing for sensitization predictions.

“Sensitization through the lung is a growing issue and methods to predict if a chemical has a sensitization effect are limited”, says Anki Malmborg Hager, CEO in SenzaGen. Based on extensive research about the responses of the immune system in allergic reactions, SenzaGen has now launched a test that predicts the respiratory sensitization ability of chemicals based on the GARD methodology.

An international scientific article about the underlying research has been published in PLOS ONE, under the title “Prediction of Chemical Respiratory Sensitizers Using GARD, a Novel In vitro Assay Based on a Genomic Biomarker Signature”. http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0118808

SenzaGen´s first product, a skin sensitization test of chemicals, is already on the market.

SenzaGen AB completes successful collaboration with Beiersdorf AG.

SenzaGen AB, a diagnostic spin-off company from Lund University, reports the successful completion of a collaboration with Beiersdorf.

SenzaGen AB, a diagnostic company working to replace animal testing, has been collaborating with Beiersdorf to evaluate its skin sensitization test for chemicals.

SenzaGen AB is based on research at the Department of Immunotechnology at Lund University, providing animal-free, in vitro sensitization tests for the cosmetic, chemical, pharmaceutical and food industries.

Beiersdorf has been working in the development and recognition of alternative methods for more than 20 years and is one of the main players in the cosmetic industry in Europe. An industry that is highly interested in recommendations in this field – especially after the ban in March 2013 on animal testing in the cosmetic industry.

“It has been very valuable for SenzaGen to be able to challenge its skin sensitization test in an industrial setting.” says Prof. Carl Borrebaeck, chairman of the board of SenzaGen.

In the collaboration, blind testing of two industrial test sets of chemicals were performed using the SenzaGen proprietary GARD assay, resulting in an accuracy of 89%.

henrik johansson senior scientist

Dr. Henrik Johansson, scientist and COO of SenzaGen AB, was awarded the LUSH Young Researcher Award 2014.

“The project for which Dr. Johansson was awarded, the Lush Prize Young Researcher Award, describes the development and use of the novel test method GARD – Genomic Allergen Rapid Detection, an assay for assessment of chemical sensitizers.

…GARD utilises an in vitro model of so-called dendritic cells, a central player in the human immune system. These cells are stimulated with any substances to be tested, and following an incubation time of 24h, the genetic material of the cells are isolated. By measurements of a certain set of genes in the cells, which could be viewed as on/off-switches of the immune response, the eventual risk of the tested substances ability to induce allergy can be predicted.” [Lush Prize Young Researcher http://www.lushprize.org/2014-prize/2014-prize-winners/]

Read more on Lush Prize Young Researcher Award web site

Pattern rules: biomarker signatures for sensitization as an alternative to animal testing

Biomarkers in Medicine, December 2011 ,Vol. 5, No. 6 , Pages 809-811
(doi: 10.2217/bmm.11.82)
Lindstedt M., Borrebaeck C.A.K.
“Identification of relevant endpoints and biomarkers is essensial for development of alternative assays predicting sensitisation. Omics-based techniques have recently generated very promising biomarker patterns, as well as pathways, which will be used in the identification of sensitising agents”

Functional and transcriptional profiling of MUTZ-3, a myeloid cell line acting as a model for dendritic cells

Immunology. 2006 Feb; 117(2): 156–166.

Larsson K., Lindstedt M., Borrebaeck C.A.K.

ABSTRACT

The incidence of allergy is steadily increasing, but the molecular mechanisms involved in the allergic immune response are still not fully understood. In particular, further investigations focusing on dendritic cells, which are central in orchestrating the immune response, are needed. The objective of this study was to investigate the ability of myeloid leukaemia-derived cell lines, such as KG-1, THP-1 and MUTZ-3, to serve as in vitro models for dendritic cells. The ability of these cell lines to mature into functional dendritic cells, expressing costimulatory molecules, was assessed by functional and transcriptional profiling and compared with that of monocyte-derived dendritic cells, which are now used as a standard source of dendritic cells. High-density microarray analysis was utilized to study the transcriptional activity and kinetics of activation of the differentiated MUTZ-3 cell line, in response to a cocktail of inflammatory cytokines. The data obtained clearly demonstrate that MUTZ-3 cells have the ability to induce antigen-independent proliferation in CD4+CD45RA+ T cells, whereas KG-1 and THP-1 only induced a marginal response. Furthermore, MUTZ-3 displayed the phenotypic and transcriptional profiles of immature dendritic cells, after differentiation with granulocyte–macrophage colony-stimulating factor and interleukin-4. Upon activation with inflammatory cytokines, MUTZ-3 matured phenotypically and exhibited a gene induction similar to that of monocyte-derived dendritic cells. This delineation of the cellular and transcriptional activity of MUTZ-3, in response to maturational stimuli, demonstrates the significance of this cell line as a model for functional studies of inflammatory responses.

Keywords: dendritic cells, myeloid cell line, high-density microarray, inflammation, allergy