Abstract 1494: IgE receptor-activated human mast cells have potent anti-cancer properties

Abstract The purpose of this study was to test the hypothesis that human mast cells (MC) have anti-tumor mediators that can be targeted to tumor specific antigens, induced to release these mediators, and cause cancer cell apoptosis. Breast cancer (BC) continues to be a significant cause of mortality for women in the United States. The oncogene HER2/neu is overexpressed in BC and is validated target for cancer therapeutics. New immunotherapy strategies and combinations of immune agents with non-redundant mechanisms of action are needed. The role of human tissue mast cells (MC) in the pathology of many cancers is not known. Nonetheless, high densities of MC are associated with favorable prognosis in certain types of cancer such as BC suggesting an anti-tumor effect. We previously reported that human adipose cells can be differentiated into autologous, fully functional MC (ADMC) capable of releasing mediators upon FcϵRI stimulation that induce BC cell death of cell suspensions of SK-BR3. Further data is presented demonstrating the anti-tumor effects of ADMC using BC tumor masses. The ADMC, sensitized with breast cancer-specific IgE anti-HER2/neu, bound to and were activated by, HER2/neu-positive human BC cells. The anti-HER2/neu IgE-sensitized ADMC bound to, infiltrated, and induced apoptosis of HER2/neu-positive BT-474 BC tumor masses as determined by time-lapse, live cell confocal imaging. Specific, HER2/neu IgE-mediated binding was also verified in vivo using immunocompromised xenograft models. Further studies are warranted to determine if tumor-targeted, autologous MC may be a new way to treat solid tumors. Citation Format: Chris Kepley, Mohammad Ferrydouni, Mona Motaghed, Kristen Dellinger. IgE receptor-activated human mast cells have potent anti-cancer properties [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1494.