Therapeutic strategies targeting B-cells in multiple sclerosis

Autoimmun Rev. 2016 Jul;15(7):714-8. doi: 10.1016/j.autrev.2016.03.006. Epub 2016 Mar 9.

Abstract

Multiple sclerosis (MS) is a chronic inflammatory and demyelinating disease of the central nervous system (CNS) that traditionally has been considered to be mediated primarily by T-cells. Increasing evidence, however, suggests the fundamental role of B-cells in the pathogenesis of the disease. Recent strategies targeting B-cells in MS have demonstrated impressive and sometimes surprising results: B-cell depletion by monoclonal antibodies targeting the B-cell surface antigen CD20 (e.g. rituximab, ocrelizumab, ofatumumab) was shown to exert profound anti-inflammatory effect in MS with favorable risk-benefit ratio, with ocrelizumab demonstrating efficacy in both relapsing-remitting (RR) and primary-progressive (PP) MS in phase III clinical trials. Depletion of CD52 expressing T- and B-cells and monocytes by alemtuzumab resulted in impressive and durable suppression of disease activity in RRMS patients. On the other hand, strategies targeting B-cell cytokines such as atacicept resulted in increased disease activity. As our understanding of the biology of B-cells in MS is increasing, new compounds that target B-cells continue to be developed which promise to further expand the armamentarium of MS therapies and allow for more individualized therapy for patients with this complex disease.

Keywords: B-cells; CD20; Multiple sclerosis; Ocrelizumab.

Publication types

  • Review

MeSH terms

  • Antibodies, Monoclonal, Humanized / administration & dosage
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • B-Lymphocytes / immunology*
  • Humans
  • Multiple Sclerosis / drug therapy
  • Multiple Sclerosis / immunology*

Substances

  • Antibodies, Monoclonal, Humanized
  • ocrelizumab