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

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.