Projects
DC4Balance
As our understanding of the immune system and its role in health and disease grows, it is becoming increasingly evident that many immune system-directed treatment opportunities for major diseases are being left on the table. To unlock immunotherapy’s full potential, we must acquire a deep understanding of how dysregulations in the delicate balance between immune activation and regulation distort host immunity and drive disease outcomes.
The goal of the DC4Balance consortium is to acquire a comprehensive view of immune dysregulation with a disease-overarching strategy. This will facilitate the development of effective, personalized immunotherapy for patients.
Towards this goal, we have now analysed patient-derived samples of clinical trials performed in cancer patients, allergic patients, and multiple-sclerosis patients. By performing the assays at specialised sites, differences caused by assay variability are minimized. Samples of patients were distributed to the respective centres, experiments were performed, and data are assembled. In the remaining project period, unbiased immune cell phenotyping will be done. By determining immune pathways, we aim to decipher the underlying pathophysiology of immune-mediated diseases, allergy, and cancer.
Furthermore, we pursued translational strategies. In experimental cell-based assays and ex vivo human studies, antigen/adjuvant containing nanoparticles were tested to steer the effect on the immune system towards immune-balance. Combinations of disease-relevant antigen and adjuvant, either immune-stimulating in case of an under-stimulated immune system (cancer) or immune-tolerizing in case of an overactive immune system (allergy, chronic inflammatory diseases) are tested and selections are made for further assessment and GMP-compliant manufacturing.
To conclude, the state-of-the-art monitoring assays employed within DC4Balance, enable’s decoding of immune system functional failure and visualize the effects of disease-overarching immune-modulation in patients. By providing scientific evidence for optimal immune-steering with nanoparticles and delivering protocols for subsequent clinical translation, novel nanotherapeutics are within reach for patients. Because immune-mediated mechanisms are present in various aspects of tissue and organ homeostasis, they are implicated in pathologies as diverse as autoimmune diseases (multiple sclerosis, rheumatoid arthritis); inflammatory and metabolic disorders (atherosclerosis, diabetes); and even chronic neurodegenerative disorders (Alzheimer’s disease, Parkinson’s disease). Hence, well-designed immune modulating nanoparticles might provide benefit for many individual patients.
Collaborators
