Ofatumumab
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Ofatumumab is an anti-CD20 antibody used for the treatment of chronic lymphocytic leukemia (CLL) in selected patients with certain treatment histories and responsiveness to anticancer medications.
Ofatumumab is an anti-CD20 antibody used for the treatment of chronic lymphocytic leukemia (CLL) in selected patients with certain treatment histories and responsiveness to anticancer medications.
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.
Ofatumumab is indicated, in combination with chlorambucil, for the treatment of previously untreated patients with chronic lymphocytic leukemia (CLL) for whom fludarabine-based therapy is considered inappropriate. In patients with recurrent or progressive CLL, ofatumumab is indicated for extended treatment of patients who are in complete or partial response after at least two lines of therapy for recurrent or progressive CLL. Ofatumumab is indicated for the treatment of patients with CLL refractory to fludarabine and alemtuzumab. Ofatumumab is also indicated for the treatment of adult patients with relapsing forms of multiple sclerosis, including active secondary progressive disease, clinically isolated syndrome, and relapsing-remitting disease.
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