Antibodies against the CD20 antigen indisputably constitute an important addition to the treatment arsenal in chronic lymphocytic leukaemia (CLL). Still, their efficacy as single agents has been somewhat disappointing. In this paper, we present data suggesting that a contributing reason for their relative inefficacy is that they trigger release of immunosuppressive reactive oxygen species from monocytes.
In fully autologous ADCC experiments with rituximab, for which NK cells, monocytes and leukemic target cells were isolated from patients with CLL, we found that antibody-triggered ROS release from monocytes interfered with NK cell function and induced substantial NK cell death. Notably, anti-oxidative agents restored ADCC and NK cell viability. In our opinion, these findings suggest that the efficacy of monoclonal antibodies may be limited by the triggering of ROS from myeloid cells, and that antibody-based treatment might gain efficacy by the addition of anti-oxidative agents, serving to protect anti-leukemic lymphocytes.