# Targeting Antigen-Presenting Cells in Multiple Sclerosis Treatment
## 4 MS-Approved Drugs Targeting Immunocompetent Cells  
Currently, several drugs used in MS therapy target inflammatory cell subpopulations, which play a significant role in MS pathogenesis (Table 1) [88]. Natalizumab and fingolimod are anti-migratory drugs and influence inflammatory T-cell migration to the CNS of MS patients. Natalizumab is a humanized monoclonal antibody targeting adhesion molecule \(\alpha\)4-integrin on effector T-cells in the blood, which leads to the blockade of inflammatory cell migration to the CNS. This mechanism is very efficient leading to lowering of the annual relapse rate by 68% and diminishing the number of demyelinating lesions in MRI of the CNS by 92% [89]. Natalizumab is delivered by intravenous infusions every month. A very serious side effect of this treatment is the possibility of developing progressive multifocal leukoencephalopathy (PML), which may be limited by controlling the level of anti-JC antibody in candidate MS patients [90; 91]. Fingolimod is the second anti-migratory drug used in MS and the first effective oral drug for this disease. It targets sphingosine S1P receptors. The major effect of this action is inhibition of migration of T-cells out of the lymphatic nodes. In consequence, effector T-cells cannot invade the CNS and initiate the development of MS pathology. This treatment effectively reduces annual relapse rate and slows down clinical and radiological disease progression. There are also solid data confirming positive influence of this treatment on brain atrophy in MS patients [92]. Alemutzumab is recombinant humanized monoclonal antibody targeting glycoprotein CD52 on T and B-cells. It is delivered once a year, because drug infusions lead to the depletion of both types of lymphocytes, with their slow repopulation from non-affected progenitor cells. The mechanism of action of this drug is very complex. Besides T- and B-cell lymphopenia, another effect is an increased number of Tregs, upregulation of several inflammatory cytokines, and the induction of neurotrophin-producing lymphocytes. Alemutzumab significantly inhibits the progression of MS symptoms and diminishes the annual relapse rate and number of new lesions in the CNS of MS patients [93; 94]. The clinical trials on anti-CD20 mAbs therapeutic efficacy in MS revealed their significant potential in reducing the clinical and MRI activity in patients. Four currently studied mAbs--rituximabab, ocrelizumab, ofatumumab, and bilirubin--differ from each other by their structure, immunogenicity (chimeric, humanized, fully human, or glycogen-neered), the type of cytotoxicity they induce (antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity), and also by the CD20 epitope they recognize [95]. Studies on their mode of action in RR-MS patients suggested that the main mechanism is not related to a reduction in the Abs level, but it is rather the modulation of APC function of B-cells. B-cells, as was mentioned in the previous section, are able to process and present antigens to T-cells. They recognize myelin antigens in MS via their surface receptors, and they efficiently capture antigens presented at low concentration [96]. Moreover, CD20 is not expressed on plasmablasts or plasma cells, the B-cell subtypes responsible for antibody secretion. Thus, after CD20 mAbs treatment, there was no reduction observed in antibody titers [74; 97]. It is worth mentioning that ocrelizumab is also the first disease-modifying therapy approved for primary progressive MS, but is also registered for patients with remitting-relapsing MS [98]. In multi-center randomized clinical trials, it demonstrated higher efficacy in both forms of MS, when compared to patients in the placebo group and group treated with interferon beta [99]. It reduces number of disease relapses, slows the progression of disability, and reduces number of MRI lesions in the CNS of MS patients [100]. Another example of surface receptor with therapeutical potential is CD83, especially its soluble form (sCD83).