Psoriceptor

Targetvalidierung: Validation of Innate Immune Receptors as targets for the treatment of psoriasis (Psoriceptors) - Haut-on-a-Chip-Systeme und Korrelation mit klinischen Daten

01.05.2020 bis 30.04.2022

The overall project addresses the need of an efficient targeted therapy against psoriasis. Psoriasis has been reported to be initiated by excessive activation of toll-like receptors (TLRs) of the innate immune system. Our strategy for the validation of TLRs as targets in psoriasis is to establish human immunocompetent in vitro disease models in a relevant setting and amena-ble for medium throughput screening of candidates. For this, both a tissue-engineering approach to generate immune competent disease models at a scale directly comparable with clinical biopsies (IGB) and Organ-on-a-chip (OoC) models will be used (UKT). We strive for a targeted immunomod-ulatory therapy, which avoids systemic application by identification and development of TLR antag-onists locally applicable to ameliorate psoriasis. TLR modulators have been identified by Fraunhofer IGB in previous projects, which are IP-protected and can be directly evaluated for their effect on psoriasis in vitro. For this purpose the UKT-Hautklinik, the UKT μOrgano Lab and the Fraunhofer IGB set up a consortium with complementary expertise, including the required clinical access to develop new treatment options for psoriasis and new enabling technologies for developing treatment of immune mediated diseases.
The key objectives of this sub-project is to transfer the 3D in-vitro psoriasis disease models estab-lished by the IGB to micro-physiological OoC platform for high-throughput screening on the one hand (UKT μOrgano Lab) and to validate these models with clinical biopsies (UKT Hautklinik) on the other hand. The OoC will be a multilayered chip system, integrating physiologically relevant components, such as an ECM-like hydrogel, endothelial cells, and vasculature-like perfusion with immune cells. The transparent character and easy accessibility of the system with selected high tech read-out methods will allow non-invasive monitoring and the investigation of the tissue in real-time. This hu-man immunocompetent Organ-on-a-chip offers a rapid screening platform for profiling of selected drug candidates, including an early on information on safety liabilities and guide the risk mitigation strategy prior the first-in-human studies. The potential of developed models relies on their quality and their ability to mimic the clinical pathologic phenotype of psoriasis. Thus, UKT Hautklinik will use biopsies from psoriatic patients to validate the relevance of these models using immunohistochem-istry and cytokine level measurements.
A central method of exploitation is the patenting and further development of the identified therapeu-tics. The Fraunhofer IGB in collaboration with the UKT Hautklinik is promoting this. In addition to the utilization of the identified therapeutics, the developed skin-on-a-chip model also has a great utiliza-tion potential. Both as a "healthy" model and as a disease model (psoriasis) there are broad appli-cation possibilities as an in vitro model for the investigation of pathophysiological basics and as a test model for toxicity and allergen examinations.