Tumor-derived exosomes (TEX) containing the neoantigen messages of the mutating cancer are harvested from a patient’s peripheral blood (or other body fluid) together with the patient’s immune cell precursors (monocytes). The monocytes are subsequently matured over a few days in culture to produce enhanced dendritic cells (eDCs) using IL-15. The patient’s exosomes are then inserted into their matured dendritic cells using flow electroporation, and the loaded dendritic cells are administered to the patient as a course of ET-08 vaccine injections. Back inside the body, the eDCs in ET-08 process the patient-specific cancer-derived genetic and protein information from the TEX to present the epitopes of tumor specific neoantigens to circulating T cells in lymph nodes, thereby activating tumor antigen specific cytotoxic T lymphocytes (CTLs) to kill any tumor cells that display those same tumor epitopes on their cell surface major histocompatibility (MHC) molecules. In addition, eDCs release chemokines and cytokines that can recruit and activate cytotoxic NK cells to also kill tumor cells.
The patient’s immune response is supported by the concomitant treatment with a checkpoint inhibitor that “removes the brakes” from the immune system, enabling it to detect and destroy the tumor (whether primary or secondary malignant cells) and promoting the patient’s return to homeostasis and health.
Depicted below: The cycle of harvesting exosomes and monocytes from the patient, culturing the monocytes into mature dendritic cells which are electroporated with exosomes, and then re-administering them to the patient together with a checkpoint inhibitor.