Abstract
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.
Highlights
Natural killer (NK) cells are a class of lymphocytes distinct from T- and B-cells and play an important role in the innate immune system for direct killing of virusinfected cells and cancer cells as well as in antibodymediated killing in antibody immunotherapy of cancer [1,2]
CD56+ and CD3− can be used as distinct surface markers for identification of human NK cells, whereas CD16 is the receptor for the Fc portion of immunoglobulin gamma (IgG Fc) (Fc RIII receptors) to mediate antibody-dependent cell-mediated cytotoxicity (ADCC)
Since both SCID strains are deficient of T- and B-cells [40,41], we concluded that impairment of NK cells significantly contributed to host resistance to Icon or antibody immunotherapy for cancer [11]
Summary
Natural killer (NK) cells are a class of lymphocytes distinct from T- and B-cells and play an important role in the innate immune system for direct killing of virusinfected cells and cancer cells as well as in antibodymediated killing in antibody immunotherapy of cancer [1,2]. NK cells are large granular lymphocytes lacking of CD3 and T cell receptors and compose about 10% - 20% of peripheral blood lymphocytes in healthy individuals [1,3,4]. They commonly express certain cell surface markers such as CD16 and CD56 in humans and NK1.1/NK-2.1 and CD49b in mice for identification and isolation of NK cells. NK cells can produce a variety of cytokines [5], e.g., interleukin-1 (IL-1), IL-2, IL-4, IL-12, IL-15, interferons (IFN), tumor necrotic factors (TNF- and ), etc These NK-producing cytokines have numerous widespread actions including direct anti-tumor effects and autochthonous NK regulation
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