Ocrelizumab

Ocrelizumab is a recombinant humanized antibody that targets CD20, a glycosylated phosphoprotein expressed on the surface of different types of B-cells. CD20 can be found on pre-B cells, naïve and memory B-cells, and it is not expressed on hematopoietic stem B-cells, pro-B cells (precursors), or differentiated plasma cells. Therefore, by targeting CD20, ocrelizumab does not affect the concentration of IgG and IgM antibodies in blood or the cerebrospinal fluid.

B-cells contribute to the pathogenesis of multiple sclerosis (MS) through the activation of proinflammatory T-cells and the secretion of proinflammatory cytokines. Also, B-cells may differentiate into plasma cells that produce autoantibodies directed against myelin, leading to the complement-mediated attack on the myelin sheath. By targeting CD20, ocrelizumab specifically depletes B-cells. While the exact mechanism of ocrelizumab leading to B-cell depletion is unknown, there are several proposed mechanisms. It has been suggested that upon cell surface binding to CD20-expressing B-cells, ocrelizumab promotes antibody-dependent cellular cytotoxicity and complement-mediated cell lysis while preserving the capacity for B-cell reconstitution and preexisting humoral immunity.