Immunoreceptors and drug screening

The innate immune system has great influence on the pathogenesis or the course of diseases such as allergies, infections, tumors, or autoimmune diseases. Central regulators of the innate immune system are various classes of immune receptors. Using whole-cell biosensor assays, we identify novel immunomodulatory molecules that are potential drug candidates for the treatment of immunological diseases.

Receptors of the innate immune system

The receptors of the innate immune system recognize conserved molecular patterns of infectious agents, but also isolated chemical structures, and are called Pattern Recognition Receptors (PRRs). Stimulation of these receptors leads to the production of proinflammatory cytokines via the activation of different signaling cascades and transcription factors, thus playing an important role in the development of pathological processes in acute and chronic inflammatory diseases in humans. Among the PRRs, Toll-like receptors (TLRs) are the largest and most well-known family.


Therapeutic approach – Agonists and antagonists of immune receptors

Therefore, agonists and antagonists are a new therapeutic approach for immunotherapy via immunomodulators. Receptor agonists stimulate the innate immune system and are often used as drug adjuvants, while antagonists inhibit inflammatory processes. The possible indications range from allergies, infections and tumors to autoimmune diseases.

Drug screening with whole-cell biosensor assay

The use of electrochemical and optical sensors can provide structural but less functional information. The latter, however, is of great importance for pharmaceutical screening since drug effects are often very complex and can only be reduced in selected cases to simple receptor-ligand interactions. For this reason, it is necessary to include whole cells or even parts of tissues in the assay. The molecules identified using the mammalian whole-cell biosensor assay at Fraunhofer IGB represent potential drug candidates for the prevention and treatment of immunological diseases.

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Reference projects

JRHDD – Joint Research Hub for Drug Discovery and Delivery

The central objective of the JRHDD project was to exploit mechanisms of innate immunity in combination with targeted drug delivery for therapy of infections as well as autoimmune and inflammatory diseases. Targeting these compounds directly to the site of infection or inflammation will support the healing process significantly. The JRHDD is continued as FPC_DD@HUJI from October 2018.

 

Duration: July 2017 – September 2018

Discovery and delivery of PRR antagonists and agonists to regulate innate immune reaction

Agonists and antagonists of TLRs are a promising new therapeutic approach for immunotherapy by using them as immunomodulators. The possible spectrum of indications ranges from allergies, infections and tumors, up to autoimmune diseases. It is the aim of this international project at Fraunhofer IGB to seek out new TLR antagonists/agonists, in order to be able to treat inflammatory reactions and allergies.

Duration: November 2012 – October 2015

PsoBiBi – Development of psoriasis therapeutics using bicyclic genetically encoded libraries

Toll-like receptors (TLR) of the innate immune system play a key role in inflammatory skin diseases like psoriasis. In the PsoBiBi project, Fraunhofer IGB identifies, synthesizes and validates TLR antagonists for topical application as an alternative to conventional treatment methods, some of which have considerable side effects.

 

Duration: November 2019 – October 2022

imSAVAR –

Immune Safety Avatar: Nonclinical mimicking of the immune system effects of immunomodulatory therapies

 

In the imSAVAR project, an interdisciplinary EU consortium is developing innovative model systems to identify side effects of immunomodulating therapeutics on the immune system and to develop new biomarkers for diagnosis and prognosis. Fraunhofer IGB is involved in the development of novel immunocompetent in vitro models based on organ‑on‑chip systems as well as of cell‑based reporter gene assays using receptors of the immune system. Furthermore, they are part of the project management team.

Duration: December 2019  – November 2025