Advanced Antigen-Specific Dendritic Cell-Based Therapy to Re-establish Tolerance in Immune-Mediated Diseases

Autoimmune diseases are currently treated with immunosuppressive and supportive therapies, which dampen inflammation, but do not stop the cause of the disease and are required life-long. Thus, there is an unmet need for safe and effective therapies for these diseases, which are well-tolerated and targeting the cause of disease. Tolerogenic dendritic (DC) cell-based therapies, offer the possibility of restoring immune regulation leading to long-lasting effects. Vitamin (Vit)D3-modified tolerogenic DC have been recently applied to Multiple Sclerosis (MS) patients in Phase I trials, demonstrating safety, tolerability, feasibility, and preliminary evidence of an effect. Molecular characterization of VitD3DC from MS patients suggests that they own less tolerogenic properties than those from healthy individuals. Thus, correcting these deficiencies through gene transfer could improve their effectiveness. The aim of IMMUTOL is the fast-track development and validation of an advanced therapeutic medicinal product (ATMP) based on VitD3-modified tolerogenic DC for immunotherapy approaches. Through a multidisciplinary approach, IMMUTOL will leverage the power of tolerogenic VitD3DC-based immunotherapy to develop a more potent and durable treatment for MS and, in turn other autoimmune inflammatory diseases with an unmet medical need. In parallel, it will bring information about tolerance mechanisms and patient-specific requirements for manufacturing effective tolDC products. Results will lead to design of a clinical protocol according to the regulatory requirements for the first-in-man application of engineered tolerogenic VitD3DC in MS patients.