Emerging monoclonal antibodies and related agents for the treatment of chronic lymphocytic leukemia

Abstract

Monoclonal antibodies (mAbs) – rituximab, ofatumumab and alemtuzumab – have been approved for use in the therapy of chronic lymphocytic leukemia (CLL). Recently, a new generation of anti-CD20 mAbs has become available for preclinical studies and clinical trials. These antibodies were engineered to have augmented antitumor activity by increasing complement-dependent cytotoxicity, antibody-dependent cellular cytotoxicity and Fc-binding affinity for the low-affinity variants of the Fcγ receptor IIIa. The most promising mAb directed against CD20 is obinutuzumab (GA-101). mAbs directed against CD22, CD37 and CD40 have also shown some activity in CLL. In addition, small modular immunopharmaceuticals – TRU-015 (anti-CD20) and TRU-016 (anti-CD37) – that retain Fc-mediated effector functions have been developed and investigated in preclinical studies and clinical trials. Antibody–drug conjugates and recombinant immunotoxins are also being evaluated in lymphoid malignancies. Further studies will elucidate the role of these agents in the treatment of CLL.