Additive cytotoxic effect of bortezomib in combination with anti-CD20 or anti-CD52 monoclonal antibodies on chronic lymphocytic leukemia cells

Inhibitor of proteasome, bortezomib (BOR), although highly active in vitro, showed unexpectedly low efficacy in vivo in patients with B-CLL when used alone. We studied the in vitro cytotoxic effects of BOR in combination with anti-CD20 (rituximab, RIT) or anti-CD52 (campath, CAM) monoclonal antibodies on B-CLL cells. Both BOR + RIT and BOR + CAM combinations exerted additive cytotoxicity, triggering caspase-dependent apoptosis. The treatment significantly modified expression of several apoptosis-regulating proteins, including upregulation of Bax or downregulation of Bcl-2 and Mcl-1 by BOR + RIT, as well as downregulation of Bcl-2 and XIAP by BOR + CAM. These data suggest the feasibility of concomitant use of those agents for the treatment of B-CLL patients.