Augmenting Trastuzumab Therapy Against Breast Cancer Through Selective Activation of NK Cells.

摘要

Trastuzumab, a monoclonal antibody (mAb) targeting HER-2/neu, kills tumor cells by several mechanisms, including antibody-dependent cellular cytotoxicity (ADCC). Strategies that enhance the activity of ADCC effectors, including natural killer (NK) cells, may improve trastuzumab s efficacy. NK cells that encounter trastuzumab-coated, HER2-overexpressing breast cancer cells become activated and express CD137, a costimulatory receptor. CD137 activation, which is dependent on the Fc RIII receptor, occurred both in vitro and in the peripheral blood of women with HER2- expressing breast cancer following trastuzumab treatment. Stimulation of trastuzumab-activated NK cells with an agonistic mAb against CD137 killed breast cancer cells more efficiently in vitro and in multiple HER2+ in vivo models.