Stimulation of natural killer cells with a CD137-specific antibody enhances trastuzumab efficacy in xenotransplant models of breast cancer

摘要: Trastuzumab, a monoclonal antibody targeting human epidermal growth factor receptor 2 (HER2; also known as HER-2/neu), is indicated for the treatment of women with either early stage or metastatic HER2(+) breast cancer. It kills tumor cells by several mechanisms, including antibody-dependent cellular cytotoxicity (ADCC). Strategies that enhance activity ADCC effectors, NK cells, may improve efficacy trastuzumab. Here, we have shown upon encountering trastuzumab-coated, HER2-overexpressing cancer become activated and express costimulatory CD137. CD137 activation, which was dependent on cell expression FcγRIII receptor, occurred both in vitro peripheral blood HER2-expressing after trastuzumab treatment. Stimulation trastuzumab-activated an agonistic mAb specific killed (including intrinsically trastuzumab-resistant line) more efficiently vivo xenotransplant models cancer, one using primary tumor. The enhanced restricted to antibody-coated cells. This sequential strategy, combining tumor-targeting second activates host innate immune system, therapeutic effects antibodies against other tumors.