A New Cellular Cancer Immunotherapy Platform Technology Using Autologous Human Adipose-Derived Mast Cells

Autologous immune cell-based therapies to re-activate the immune system have been developed to treat patients with cancer. For example, chimeric antigen receptor T cell (CAR T) therapy is an FDA approved strategy that uses autologous T cells as a cancer treatment. Mast cells (MC) are important immune sentinels and widely recognized for their role as mediators of Type I hypersensitivity. However, they also secrete anti-cancer mediators such as tumor necrosis factor alpha (TNF-α) and granulocyte-macrophage colony-stimulating factor (GM-CSF) which are being investigated in clinical trials for cancer treatment. We generated adipose-derived mast cells (ADMC) and sensitized with anti-CD20 IgE antibodies and challenged with B-lymphoma cells. In addition, immunocompromised mice were examined for the maximal tolerated dose using ADMC. The ability of the ADMC to be transduced with lentiviral vectors carrying green fluorescence protein was examined. It is shown that CD20 IgE-sensitized ADMC bind to and are activated by CD20 positive B-lymphoma cells. The ADMC injected into mice do not display signs of anaphylaxis by the systemic injection of up to 1 × 106 ADMC/mouse. It is also shown for the first time that ADMC and their adipose-derived stem cell precursors can be transduced with a lentiviral vector carrying green fluorescence protein without affecting function. This discovery indicates the ADMC could be transduced with other tumor killing molecules to create a “super killing” cell with potent and diverse anti-tumor activity. Using tumor targeting IgE’s, autologous ADMC could be used as a “Trojan Horse” to deliver these anti-tumor mediators to tumors and serve as a new cancer immunotherapy platform.