- Development of new immunotherapies for autoimmunity and transplant rejection.
- Providing non-human primates for safety evaluation of immunotherapies.
- Developing and improving disease models for therapy evaluation.
- Development and improvement of non-invasive methods to assess disease markers.
- Development of in vitro parameters to predict in vivo outcome of immunotherapy.
- Providing adequate disease models for therapy efficacy evaluation.
Biotechnology has made the development of novel biological therapeutics possible. These new compounds act very specifically and often show a high degree of species specificity. Therefore preclinical efficacy and safety evaluation can best be carried out in nonhuman primates. The immune system of non-human primates shows a much better similarity to the human immune system that non-primate species such as rodents. Therefore, results on the evaluation of new immunotherapies obtained in non-human primates have the best predictive value for the clinic. Relevant models which allow evaluation of immunotherapy are already available such as arthritis, multiple sclerosis, skin and organ transplantation, or will be further developed. The immunotherapeutic strategy that will be employed in this project is to investigate the efficacy and safety of immuno-manipulation at several levels in the immune system:
1) At the level of antigen recognition (the Mhc-antigen-TCR (T cell receptor) trimolecular complex);
2) At the level of the co-stimulatory pathways, eg. B7-CD28, CD40 ligand-CD40, LFA-1 ICAM-1/-3 formation;
3) At the level of soluble messenger molecules, such as cytokines TNFa, IFNa, etc.
The aim will be induction of permanent tolerance to self, allo- (and xeno-) antigens, without impairment of the immune system's capacity to combat pathogens.
The participants will develop these new approaches and promising therapeutics will be evaluated in relevant animal models in the Centralized Facility for Immunotherapy Evaluation in nonhuman primates. As single approaches may not be sufficient for tolerance induction in an already ongoing disease, combinations of immunotherapies will be constructed to interfere at different levels of the immune response.
The aim of the Centralized Facility will be to provide the relevant animal models, as well as the corresponding knowledge for preclinical evaluation of novel immunotherapies, which can otherwise not be developed for clinical application.