Fig. 5

Schematic diagram depicting ongoing antigen-specific immunotherapies for multiple sclerosis. a Peptide and protein-based approaches include the use of whole antigens, unaltered myelin peptide ligands, altered peptide ligands (APLs), and soluble myelin peptide–MHC complexes. b The DNA vaccination approach relies on a bacterial plasmid carrying a gene encoding a specific antigen peptide. Peptide-loaded carrier approaches can be divided into biological and synthetic methods. c Biological carrier approaches induce tolerance by using cells or extracellular vesicles (EVs) as carriers, such as autologous peripheral blood mononuclear cells (PBMCs) or erythrocytes loaded with multiple sclerosis (MS) autoantigen peptides. d Synthetic carrier approaches, on the other hand, use drug delivery nanosystems to transport antigenic molecules to target tissues, including pegylated gold (PEG) nanoparticles (NPs), mannosylated NPs, polylactide-coglycolide (PLGA) NPs, and phosphatidylserine (PS) NPs, as well as peptide‒MHC complex-loaded NPs and peptides conjugated to antibodies. e Cellular immunotherapy approaches involve immunization with autologous attenuated autoreactive T cells, the use of autologous tolerogenic dendritic cells (tolDCs), and engineered Treg cells expressing myelin-specific chimeric antigen receptors (CARs). These therapies aim to induce an anti-inflammatory microenvironment; promote the secretion of cytokines such as IL-10, TGF-β, and IL-35; induce T-cell anergy; and generate Treg cells, IL-10⁺ regulatory CD4⁺ T-cell type 1 (Tr1) cells, and B regulatory (Breg) cells, ultimately suppressing autoreactive attack and restoring immune tolerance at the central nervous system (CNS) level. Abbreviations: BBB, blood–brain barrier; tolAPC, tolerogenic antigen-presenting cell; Ag, auntoantigen; Immunomod; immunomodulator. Created in https://BioRender.com