The mechanism of action of anti-CD20 monoclonal antibodies used in the treatment of multiple sclerosis

Abstract

CD20 is a transmembrane molecule located on the surface of a major population of cells belonging to the B lymphocyte lineage. Although the significance of this protein remains unknown, the presence of CD20 is a marker for mature circulating B cells. Monoclonal antibodies against CD20 are able to quickly and effectively eliminate circulating B lymphocytes. Four different anti-CD20 antibodies have been studied in the treatment of multiple sclerosis: rituximab, ocrelizumab, ofatumumab and ublituximab. Although all these monoclonal antibodies bind to the same protein, they have different molecular and pharmacological characteristics. One of the important differences between these molecules is the degree of humanisation of their molecular structure, as well as the mechanism of B cell removal. Phase III multicentre clinical trials conducted with each of these antibodies consistently confirmed that the elimination of B cells is an effective method of slowing down the progression of multiple sclerosis. Thus, B cells are considered as main group of immune cells involved in the development and course of multiple sclerosis. Numerous in vitro and in vivo data confirm the involvement of these cells in the pathogenesis of multiple sclerosis, despite the lack of evidence for the presence of pathogenic autoantibodies in this disease. Nevertheless, B cells represent a mixture of cell populations with different immunomodulatory properties. Therefore, future multiple sclerosis therapies should target the pathogenic groups of B lymphocytes, rather than non-selectively eliminating the entire population of these cells.