Natural killer (NK) cells play an important role in innate immunity and in mediating antibody and Icon (an antibody-like factor VII/IgG1 Fc immunoconjugate, which, to our best knowledge, was the first therapeutic agent for dual targeting of both the tumor cells and tumor angiogenic endothelial cells) for cancer immunotherapy. However, a common yet often neglected observation and challenge in antibody immunotherapy is that NK cells are often impaired in cancer patients. Here we hypothesize that the impairment of NK cells significantly contributes to host resistance to antibody immunotherapy for cancer. In order for antibody and Icon to achieve their optimal therapeutic efficacy, we briefly reviewed the current strategies to enhance NK activity, including infusion of cytokines, vaccines or NK cells, and the use of dietary supplements. Moreover, from our point of view we identified some remaining challenges and propose to combine these NK-enhancing strategies with Icon or antibody to overcome NK impairment and ultimately to optimize the efficacy of Icon and antibody immunotherapy for cancer.
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