In this study, a combination of the tumour-targeting antibody trastuzumab (which is specific for human epidermal growth factor receptor 2 (HER2)) and a natural killer (NK) cell-activating antibody specific for CD137 is shown to be highly effective in treating breast cancer. Trastuzumab leads to the elimination of HER2+ breast cancer cells mainly through antibody-dependent cell-mediated cytotoxicity by NK cells. NK cells exposed to trastuzumab-coated HER2+ tumour cells upregulate the co-stimulatory molecule CD137, and subsequent treatment with a CD137-specific agonistic antibody improved their ability to kill trastuzumab-coated HER2+ tumour cells in vitro. Moreover, athymic mice (which lack T cells but have normal NK cells) that were engrafted with human breast cancer cells and treated with trastuzumab followed by the CD137-specific antibody showed a marked reduction in tumour size and mortality compared with mice treated with only one antibody. The enhanced cytotoxicity was restricted to antibody-coated tumour cells, which suggests that this combined therapy could be applicable to other cancer-targeting antibodies.
ORIGINAL RESEARCH PAPER
Kohrt, H. E. et al. Stimulation of natural killer cells with a CD137-specific antibody enhances trastuzumab efficacy in xenotransplant models of breast cancer. J. Clin. Invest. 122, 1066–1075 (2012)Article
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Bird, L. A killer combination. Nat Rev Immunol 12, 231 (2012). https://doi.org/10.1038/nri3204