Ublituximab

B-cell dysregulation underlies the pathogenesis of various cancers and autoimmune conditions such as multiple sclerosis, neuromyelitis optica spectrum disease, and myelin oligodendrocyte glycoprotein IgG-associated disease. CD20 is an antigen expressed on pre-B cells, immature/mature B-cells, memory B-cells, and a subpopulation of CD3-positive T cells. Anti-CD20 antibodies can therefore induce B-cell depletion through direct cell death, induction of complement pathways, and Fc-gamma receptor (FcγR)-mediated phagocytosis (antibody-dependent cellular cytotoxicity, ADCC).

Although several anti-CD20 antibodies have been developed, therapy has been hampered by low CD20 expression by malignant cells in diseases such as B-cell chronic lymphocytic leukemia and suboptimal antibody-dependent cytotoxicity. Ublituximab binds to an epitope on CD20 distinct from that bound by other approved antibodies such as rituximab, ofatumumab, obinutuzumab, and ocrelizumab, with a similar binding constant to rituximab. Uniquely, ublituximab is produced in the rat YB2/0 cell line such that it has a low fucose content (24% compared to 93% for rituximab), improving its interaction with FcγR, especially FcγRIIIA (CD16) expressed by natural killer cells and macrophages. This difference grants ublituximab enhanced ADCC, including for low CD20-expressing malignant cells.

The precise mechanism of action of ublituximab in the treatment of multiple sclerosis is unclear, but is presumed to involve CD20 binding and subsequent cell lysis as described above.