Ofatumumab

CD20 is expressed on normal pre-B lymphocytes and mature B lymphocytes, as well as malignant B lymphocytes. Numerous studies demonstrate that the depletion of B-cells can significantly alleviate symptoms of many forms of leukemia and lymphoma, which are malignancies associated with B-cell dysfunctions and high expression of CD20.

Ofatumumab is an anti-CD20 monoclonal antibody that binds to the small and large extracellular loops of the CD20 molecule. The Fab domain of ofatumumab binds to CD20, and this drug-target interaction does not result in immediate shedding and internalization of CD20 from the plasma membrane of B lymphocytes. This allows ofatumumab to persist on the B lymphocyte cell surface for an extended period and recruit immunological molecules or FcR-expressing innate effectors, such as macrophages, that mediate immune effector functions with strong cytotoxic effects. These immune effector functions include complement-dependent cytotoxicity (CCD) and antibody-dependent cellular cytotoxicity (ADCC), which promote the lysis of malignant B-cells. Complement-dependent cytotoxicity (CDC) involves translocation of the CD20 molecule into lipid rafts, which are involved in cell signalling and receptor trafficking.

The mechanism by which ofatumumab exerts a therapeutic effect in multiple sclerosis patients is unknown but is presumed to still occur as a consequence of its ability to bind CD20.