Antigen-specific cellular therapy for MS patients: Induction of tolerance by autologous myeloid dendritic cells treated with vitamin D3 and loaded with myelin peptides

International Congress on Neuroimmunology and Therapeutics

DoubleTree by Hilton Hotel San Francisco Airport, San Francisco, CA, USA

Mª José Mansilla

Posters-Accepted Abstracts: J Neurol Disord

Abstract :

Multiple sclerosis (MS) is a chronic inflammatory and demyelinating disease of the central nervous system. Current treatments for MS patients consist in non-specific immunomodulatory drugs with moderate efficacy and some important associated side effects. In the way to restore the tolerance against myelin peptides that has been lost in MS patients, efforts have been directed to new cell therapy treatment approaches. In this sense, the efficacy of different tolerogenic cells (regulatory monocytes and T cells monocytes, and tolerogenic dendritic cells) have been evaluating for autoimmune diseases such as diabetes, arthritis rheumatoid and MS. In our laboratory, we have generate functionally stable tolerogenic dendritic cells (tolDC) from MS patients by treating monocyte-derived DC with vitamin D3 (1,25(OH)2 D3) and using a cytokine cocktail (TNG-a, IL-1b and PGE2) as maturation stimulus. These tolDC loaded with a pool of seven immune-related myelin peptides induced antigen-specific and stable hyporesponsiveness in autologous myelin-reactive T cels in vitro. In addition, in vivo efficacy of murine antigen specifictolDC have also demonstrated in the animal model of MS, the experimental autoimmune encephalomyelitis (EAE) resulting in EAE prevention and transient reduction of clinical signs in mice treated therapeutically. Currently, we are working to initiate in 2016 a phase I clinical trial using myelin peptides-loaded tolDC in MS patients.