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Ofatumumab is an anti-CD20 antibody recently approved for treatment of fludarabine and alemtuzumab refractory chronic lymphocytic leukemia (CLL); it mediates much stronger complement-dependent cytotoxicity (CDC) than rituximab. Human CD59, a key membrane complement regulator that inhibits CDC, is highly expressed in B-cell malignancies and its upregulation is an important determinant of the sensitivity of B-cell malignancies to rituximab treatment. Previously, we have shown that the potent CD59 inhibitor rILYd4 sensitizes rituximab-resistant lymphoma cells to rituximab-mediated CDC. Here, we further investigated whether rILYd4 can sensitize B-cell malignancies to ofatumumab-mediated CDC and whether either ofatumumab-mediated CDC or rILYd4-enhanced ofatumumab-mediated CDC correlates with CD20 or CD59 expression, known biomarkers involved in rituximab activity.

clinical cancer research

rILYd4, a Human CD59 Inhibitor, Enhances Complement-Dependent Cytotoxicity of Ofatumumab against Rituximab-Resistant B-cell Lymphoma Cells and Chronic Lymphocytic Leukemia