Autoimmunity & Inflammation
Autoimmune diseases occur when the immune system mistakenly attacks healthy cells and tissues in the body. These diseases are diverse and can affect various organs and systems, leading to chronic inflammation and damage.
Our team possesses extensive expertise in target validation and executing fully integrated drug discovery projects, specializing in indications such as rheumatoid arthritis, systemic lupus erythematosus, inflammatory bowel disease, atopic dermatitis, and multiple sclerosis. Over the course of 15+ years, we have developed a comprehensive portfolio of predictive in vitro assays and in vivo models, gaining expertise across various target classes, including GPCRs, ion channels, transporters, enzymes, protein-protein interactions, and cytokines.
Figure 1
BRGSF transgenic mice display high immunodeficiency due to Rag2, IL-2Rγc and Flk2 genes knockout. Human CD34+ hematopoietic stem cell engraftment in these mice results in long-term humanization level for both lymphocyte and myeloid compartments. The above study is an example of humanization of a classical in vivo system for studying T cell activation by treating with a human anti-CD3 antibody. Evotec is investing continuous efforts for humanization of both mechanistic and disease models.
To enhance our capabilities, we incorporate cutting-edge CRISPR technology to knock out genes in primary human immune cells, particularly T-cells and monocytes, to validate our disease hypotheses. Recognizing the translational limitations between rodent and human immunity, we have developed and leverage pharmacodynamic mouse models with a 'humanized' immune system, enabling more robust target validation.
Figure 2
CRISPR-editing in primary human Tregs. Purified nTregs were in vitro expanded before CRISPR/Cas9 editing. FACS plots show the reduction in FoxP3 expression after targeted CRISPR (right plot) compared to non-targeted CRISPR control (left plot).
In conjunction with these models, we utilize our biobank of primary human samples, allowing us to compare cellular responses between healthy individuals and patients with autoimmune diseases. This valuable resource enhances our understanding of disease mechanisms and aids in the identification of potential therapeutic targets. Partnering with Evotec grants access to our highly dedicated scientists, who possess expertise in cutting-edge technologies, diverse target classes, and various treatment modalities. We are well-positioned to form successful collaborations, as demonstrated by recent partnerships focused on autoimmunity and chronic inflammatory states with organizations such as UCB, Padlock, Almirall, Exscientia, Related Sciences, Dundee University, and Imidomics.
By combining our extensive experience in target validation, our comprehensive portfolio of assays and models, and our utilization of advanced technologies like CRISPR, pharmacodynamic mouse models, and primary human samples, we are committed to advancing drug discovery efforts in the field of autoimmune diseases and chronic inflammation.
Contact Our Experts
