Abstract 2547: A potential new autologous mast cell cancer immunotherapy

Abstract

Abstract Mast cells (MC) are important immune cells that reside in tissue and are most widely recognized for their role as mediators of Type I hypersensitivity reactions (allergies). In certain cancers, such as breast cancer, the presence of MC in the tumor microenvironment has been associated with favorable prognosis, which may be due to their ability to release, through activation of the high affinity IgE receptor FcεRI, anti-tumor mediators such as tumor necrosis factor alpha (TNF-α) and granulocyte-macrophage colony-stimulating factor (GM-CSF). Thus, developing approaches to target autologous MC to tumor antigens is a potential new form of cancer immunotherapy. However, this concept has not been realized given that MC reside in tissue; thus, efficient removal, expansion ex vivo, and targeting to tumor sites has not yet been feasible. Previous attempts to generate MC from human progenitor cells have yielded cells that are often immature and not optimally functional. We report here, for the first time, the generation of functional human MC from adipose tissue in numbers sufficient for clinical applications. The adipose derived MC (ADMC) are phenotypically similar to connective tissue MC as evidenced through their expression of tryptase, chymase, c-kit, and FcεRI. The ADMC release several anti-tumor mediators through FcεRI activation. The ADMC, sensitized with an anti-HER2/neu IgE with human constant regions, bound to and were activated by HER2/neu-positive human breast cancer cells (SK-BR-3). ADMC sensitized in this way were observed to induce apoptosis in breast cancer cells when co-cultured. Importantly, breast cancer cell apoptosis was also observed after addition of media containing mediators released from activated ADMC. In conclusion, we present a novel method for the production of functional human MC from adipose tissue and demonstrate that these cells can be directed to target and eliminate breast cancer cells. It may now be possible to use them in conjunction with IgE antibodies targeting cancer cells for autologous mast cell cancer immunotherapy (AMCIT) as a new way to treat solid tumors such as those overexpressing HER2/neu for which new therapies are urgently need. Citation Format: Jesse D. Plotkin, Michael G. Elias, Tracy R. Daniels-Wells, Anthony Dellinger, Manuel L. Penichet, Christopher L. Kepley. A potential new autologous mast cell cancer immunotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2547.