UCLA

Type-I hypersensitivity is a mast cell-mediated degranulation process induced by IgE-antigen recognition. Inspired by this feature, we genetically modified mouse mast cell line MC/9 to overexpress perforin and granzyme B (PG-MCs) with lentiviral particles. In our melanoma model utilizing B16 cells expressing membrane-bound OVA, we observed a polarized degranulation of mast cells towards cancer cells upon the recognition of antigens by anti-OVA IgE. PG-MCs could selectively kill cancer cells via IgE-antigen recognition. The IgE-sensitized PG-MCs administered through an intertumoral route successfully delivered perforin and granzyme B toward target cells to induce anti-tumor efficacy. Moreover, we demonstrated the tuning effect of tumor microenvironment by mast cell-induced hypersensitivity, skewing the tumor milieu toward a ‘hot’ state with more lymphocyte infiltration. In addition, this mast cell therapy, in combination with 5- fluorouracil (5-Fu), induced a more pronounced inhibition of tumor growth, which is likely associated with the depletion of myeloid-derived suppressor cells (MDSCs).