Killing of CLL and NHL cells by rituximab and ofatumumab under limited availability of complement

Rituximab and ofatumumab are anti-CD20 antibodies applicable to treatment for non-Hodgkin's lymphoma and chronic lymphocytic leukemia (CLL). Effectiveness of both immunotherapeutics may depend on exhaustible complement system. To model the efficacy of complement usage by ofatumumab and rituximab under limited complement availability, we compared complement-dependent cytotoxicity exerted by these antibodies at low (5 and 10 %) and physiological (50 %) serum concentration in twelve CD20-positive cell lines and six freshly isolated CLL cells. Simultaneously, we assessed the expression of CD20 and membrane-bound complement inhibitors. Ratios of CD20 to CD59 and/or CD55 distinguished highly sensitive cells lysed equally efficient by both antibodies from the moderately sensitive cells, which were killed more efficiently by ofatumumab.