Enhancement of antibody-dependent cell mediated cytotoxicity: a new era in cancer treatment

The therapeutic efficacy of some anti-tumor monoclonal antibodies (mAbs) depends on the capacity of the mAb to recognize the tumor-associated antigen and induce cytotoxicity via a network of immune effector cells. This process of antibody-dependent cell-mediated cytotoxicity (ADCC) against tumor cells is triggered by the interaction of the fragment crystallizable (Fc) portion of the mAb with the Fc receptors on effector cells like natural killer cells, macrophages,gamma d T cells, and dendritic cells. By augmenting ADCC, the antitumor activity of mAbs can be significantly increased. Currently, identifying and developing therapeutic agents that enhance ADCC is a growing area of research. Combining existing tumor-targeting mAbs and ADCC-promoting agents that stimulate effector cells will translate to greater clinical responses. In this review, we discuss strategies for enhancing ADCC and emphasize the potential of combination treatments that include US Food and Drug Administration-approved mAbs and immunostimulatory therapeutics.