Coordinators: R. Ludwig (UzL), M. Peipp (CAU), G. Riemekasten (UzL)
TI-4 examines the mechanisms of disease-causing autoantibodies in order to identify new and individual therapeutic targets. Autoantibodies can cause local damage through the formation of immune complexes and the activation of the innate immune system. However, they can also occupy so-called G-protein-coupled receptors and influence their mode of operation.
In order to selectively switch off disease-causing autoantibodies, you can selectively remove them, influence their effect - particularly in the case of receptor-activating antibodies - or intervene in their formation. Bispecific monoclonal antibodies and genetically modified T-cells could represent a way to prevent specific B-cells and thus also the formation of autoantibodies. The members of TI-4 have already done some preparatory work on these possibilities and developed new disease models.
Within three years, the members want the development to have sufficiently progressed to such an extent that they can introduce new treatments in the hospital, and advance to "Clinical Demonstrator". Everyone in the team has several innovative approaches which partially complement each other and which are also at different stages. Using innovative approaches, the researching clinicians want to improve the situation of their patients with rare diseases that have previously not been adequately treatable.
The interdisciplinary networking, the coming together of rare expertise, the new and innovative approaches to research, the existence of new animal models - and even new disease models - developed by the members, not only as a result of assistance from the cluster structures, allows the translation of approaches into practice to take place in a very goal-oriented manner, and thus new pathways can be pursued. The research results can be harnessed directly by companies and help to ensure that we understand diseases better.
According to the members, certain autoantibodies or autoantibody signatures shape the individual clinical progression of a wide range of diseases, and not just those which are designated as autoimmune diseases. Recently, the researchers were able to identify a physiological network of autoantibodies, modified by age, gender and disease, and possibly also by environmental factors. Accordingly, autoantibodies are key to precision medicine and the objectives of the cluster.
The influence on the autoantibodies investigated by TI-4 through the microbiome and nutrition (in cooperation with RTF II and RTF IV), the effect of the autoantibodies on cellular signatures and on the initiation of inflammation (in cooperation with RTF III), as well as on the generation of numerous chemical messengers (RTF VI, proteome), and the visualization of the antibody effects (RTF VII) requires broad cooperation between cluster members. The complexity of the data requires good bioinformatics (RTF VIII), the optimal translation into daily practice requires the inclusion of RTF IX (ethics and economics) and access to the right group of patients (RTF X), for which the cluster provides optimum conditions through the creation of appropriate structures. New developments by other TIs and CDs will be adopted and adapted wherever possible, so that further synergies can arise.