Skimune® - Sensitisation & Immunotoxicity

Our human tissue explant assay for the detection and characterisation of adverse immune reactions in vitro.

Helping you characterise immune reactions to your novel chemicals, pharmaceuticals, biologicals and cellular therapies

Overview of Skimune®

Histopathological analysis is performed on the skin, and damage graded from I-IV
ELISA/ multiplex MSD/ Luminex analysis of culture supernatants
qPCR / mRNA expression
High throughput RNAseq analysis
Immunohistochemistry
Figure 1 – Overview of Skimune® human tissue assay system. Isolated monocytes from our volunteer blood samples are used to produce dendritic and T-cell populations. The test articles are exposed to the dendritic cells potentially maturing them. These dendritic cells are then co-cultured with autologous T-cell populations to produce a T-cell mediated reponse. These cells are finally co-cultured with the autologous skin explant in order to assess lymphocyte mediated tissue damage. This damage can be characterised though histological assessment, IHC, qPCR among many more!

Skimune® assay

What you may not have known is that Alcyomics’s Skimune® assay is a human tissue explant assay which includes activated autologous dendritic cells and T-cells to measure T-cell proliferation and cytokine release. We have further developed out assay to test for sensitisation and immunotoxicity in the skin and as a test for more general systemic immune responses.

Our assay can characterise immunological reactions in a wide range of applications such as chemicals, cosmetics, pharmaceuticals, cellular therapies and biologicals (monoclonal and Bispecific antibodies). Our assay has been widely published and validated to give you clinically relevent insights into the immunotoxiciy characteristics of your test articles. Get in touch to find out more!

Benefits of Skimune® are:

Primary human tissue-based from varied donors, allowing for a more detailed understanding of immunotoxicity across age groups, sex and other demographics.
Does not rely on 2D cultures of cells.
Our dynamic assay is capable of a wide array of readouts. Specifically, Skimune® can cover both key event 2, 3 and 4 in the sensitisation pathway (Figure 3).
Saves time and money in product development compared to other available tests.
Capable of distinguishing the type of hypersensitivity reaction.
Validated to be sensitive against: Chemicals, Complex formulations,
 Cosmetics, Biologicals, Cellular Therapies and many more.
Get in touch
Immunotoxicity assessment is a huge consideration when developing a new pharmaceuticals intended for use in humans. Are 2D cell based systems enough to truly model immunotoxicity?
Figure 3 – Skimune® fits into the current OECD sensitisation guideline process covering multiple key events.​ Our assay is able to provide data for keratinocyte responses, dendritic cell activation, T cell proliferation and organ tissue reponses.

2D OECD guideline tests

How do our assays compare with others available on the market?

Currently the gold standard techniques to determine skin sensitisation rely on a best 2 of 3 approach from the following OECD assays (Figure 4);

Key event 1 – Molecular initiating event. The Direct Peptide Reactivity Assay (DPRA) is an in chemico method, using synthetic peptides to determine protein reactivity.

Key event 2 – Keratinocyte inflammatory responses. The KeratinoSens assay uses a genetically modified immortalised cell lineage in a 2D system. Increased fluorescence from a Luciferase reporter gene allows for quantification of inflammatory upregulation

Key event 3 – Activation of Dendritic Cells (DC). The h-CLAT assay uses a human leukaemia cell line to mimic DC activation measured through changes in surface marker expression.

As a field do we need to move away from the use of genetically modified cancer cell 2D cultures for our sensitisation assessments?

Here at Alcyomics, we would argue yes. For a number of key reasons;
  • Cancer lineages contain variable genetic abnormalities which can be detrimental to cellular function.
  • Cell lines are homogenous and do not represent the heterogeneity of sensitisation responses present at a population level. Would you trust the safety of a drug if it had only been tested on a single donor?
  • 2D cell cultures have been shown to be less physiologically relevant at both the genetic and proteome level. Recent understandings have shown that a cells shape can have significant effects on its function and differentiative potential

Overview of the approach

Figure 4 - Overview of the OECD test guideline approach for sensitisation.
What about animal studies?
Other animal based immunotoxicity assays such as the local lymph node assay (LLNA) have been used extensively in the past to determine immunotoxicity in human drugs. However, these assays have been demonstrated to suffer from several disadvantages such as false positive responses, variability due to the vehicle used, their overall predictivity (~72% against human data) and their inability to distinguish between type of hypersensitivity response.

Other Immunotoxicity Testing Platform Solutions

Skimune® - Sensitisation & Immunotoxicity

Read more

T-cell proliferation & Cytokine analysis

Read more

Get in touch

How can we assist?