Toll-like receptors: a target for many therapeutic applications
Toll-like receptors (TLRs) form a class of proteins that play an important role in the innate immune system, important in host defense against infections. Moreover, TLRs play a role in other immunological processes and disruption may lead to various diseases like rheumatoid arthritis, COPD and Crohn's disease. Within this project the opportunities for TLRs as a drug-target are explored.

The broad interest for the role of the TLR protein family has led to TI Pharma's largest project, in which scientists from many different disciplines participate. Some work on the development of tools that can modulate the function of TLRs. For instance, probiotics are being selected and small molecules are being generated that specifically affect TLR activity. Also, the possibilities for improvement of vaccination strategies using TLRs are being explored. Other researchers investigate the role of TLRs in specific disease areas like cancer, cardiovascular and autoimmune disease. The knowledge obtained through this type of basic research together with the tools developed to interfere in TLR functioning will provide insight in the possibilities for further drug development based on TLR signaling.

Fast facts
Full project title: Exploitation of toll-like receptors in drug discovery
Start date: March 2008
End date: March 2012
Goal: Identifying and making toll-like receptor modulators and developing potentially relevant therapeutic applications
Principal investigator: Anja Garritsen, MSD
Project size: 41 FTE's
Background: Innate immune system
Partners: ISA Pharmaceuticals, Leiden University, Leiden University Medical Center, Maastricht University, Danone Research, MSD, Radboud University Medical Center, TNO, University Medical Center Utrecht 


The innate immune system is important for the host defense against infection by other organisms. The system provides immediate defense, but it does not result in long-lasting immunity against the source of the infection. In other words, the innate system does not develop over time, in contrary to the adaptive immune system. 

During infection, the innate immune system recruits immune cells to the site, activates a number of processes to identify the cause of infection (f.e. bacteria) and subsequently ensures these are removed. Finally, the innate immune system activates the adaptive immune system to accomplish immunity for future infections.

PhD theses from this project

Daphne de Groot  (project D1-101)
Inflammatory processes during arteriogenesis

Marcel Schijf (project D1-101)
Environmental modulation of mucosal immunity

Susanna Commandeur (project D1-101)
Facing the phases of Mycobacterium tuberculosis

“Running public-private partnerships is a profession by itself. TI Pharma is an excellent example of how you can do this in an effective way.”

Hugo Hurts
Director/Secretary of the Medicines Evaluation Board

Hugo Hurts
Director/Secretary of the Medicines Evaluation Board

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