Antigen-specific cell therapy: Myelin Peptide - Loaded Tolerogenic Dendritic Cells for Multiple Sclerosis

Abstract

Multiple sclerosis (MS) is a multifactorial disease characterized by immune dysregulation, neurodegeneration, and failure of the central nervous system (CNS) repair mechanisms. Identifying specific myelin-derived peptides as important targets of the autoreactive immune response has opened the possibility to develop antigen-specific therapeutic approaches. Dendritic cells (DCs) are the most potent professional antigenpresenting cells (APCs) of the immune system capable of inducing or suppressing the T cell response, their effect depends on different factors such as the degree of maturity, signals obtained from the local microenvironment, communication with other immune cells or the DCs subtype. Therefore, DCs have proved to be one of the most promising tools in immunotherapy in order to modify the immune response and restructure immune tolerance. There are some established protocols in vitro for generating monocyte-derived tolerogenic-DCs (tol-DCs) that exhibit numerous immunosuppressive mechanisms. However, the therapeutic potential of DCs has not yet been fully exploited clinically. In this report, I describe the immunopathogenesis of MS, different subsets of DCs, the central role of DCs in the initiation of antigen-specific tolerance, and protocols for generating tol-DCs. In addition, I will discuss the characterization of tol-DCs for clinical application, as well as recent clinical trials based on tol-DCs to treat MS.