Abstract
Multiple sclerosis (MS) is an autoimmune disease of the central nervous system and is considered to be the leading non-traumatic cause of neurological disability in young adults. Current treatments for MS comprise long-term immunosuppressant drugs and disease-modifying therapies (DMTs) designed to alter its progress with the enhanced risk of severe side effects. The Holy Grail for the treatment of MS is to specifically suppress the disease while at the same time allow the immune system to be functionally active against infectious diseases and malignancy. This could be achieved via the development of immunotherapies designed to specifically suppress immune responses to self-antigens (e.g., myelin antigens). The present study attempts to highlight the various antigen-specific immunotherapies developed so far for the treatment of multiple sclerosis (e.g., vaccination with myelin-derived peptides/proteins, plasmid DNA encoding myelin epitopes, tolerogenic dendritic cells pulsed with encephalitogenic epitopes of myelin proteins, attenuated autologous T cells specific for myelin antigens, T cell receptor peptides, carriers loaded/conjugated with myelin immunodominant peptides, etc.), focusing on the outcome of their recent preclinical and clinical evaluation, and to shed light on the mechanisms involved in the immunopathogenesis and treatment of multiple sclerosis.
Highlights
The present study attempts to highlight the various antigen-specific immunotherapies developed so far for the treatment of multiple sclerosis, focusing on the outcome of their recent preclinical and clinical evaluation, and to shed light on the mechanisms involved in the immunopathogenesis and treatment of multiple sclerosis
The present paper aims to extensively review the different, recently developed myelin antigen-specific strategies for the prevention/treatment of Multiple sclerosis (MS), especially with respect to their in vivo and clinical evaluation outcomes and the challenges they face in order to be translated to MS patients
Several exciting vaccination strategies targeting the induction of antigen-specific immune tolerance in MS have been developed during the last decades, based on a single epitope or cocktails of immunodominant epitopes of myelin proteins, altered peptide ligands, Deoxyribonucleic acid (DNA) vaccines, tolerogenic dendritic cells (DCs) pulsed with myelin peptides, attenuated autologous myelin reactive T cells, T-cell receptor (TCR) peptide vaccines, conjugates of autoantigens with various types of cells, and different types of carriers associated with myelin epitopes
Summary
Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) caused by genetically-predisposed hosts by infectious and environmental factors which induce complex autoimmune responses in the CNS resulting in degeneration of the myelin sheath and axonal loss in the brain and spinal cord [1,2,3,4,5,6,7,8,9,10,11,12,13,14] It is the most prominent demyelinating disease leading to progressive clinical disability in MS patients [5,6,15] due to ineffective remyelination [13,15]. Publications addressing pre-clinical and clinical evaluation of antigen-specific immunotherapies for multiple sclerosis were selected for inclusion
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