Reprogramming Exosomes for Novel Immunotherapy of Triple Negative Breast Cancer

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Abstract Triple negative breast cancer (TNBC) accounts for approximately 15-20% of breast cancers and is the most aggressive subtype of breast cancer. Given little efficacy for existing therapeutic regimens against a significant number of TNBC patients and continuously developed resistance of TNBC cells to chemotherapy, novel treatment strategies with significantly enhanced potency and safety are still urgently required to address unmet medical needs. Exosomes are natural membranous vesicles secreted by many types of cells and possess many important and invaluable features for drug development. By harnessing these unique biological and pharmacological properties of exosomes, we are aimed to develop innovative synthetic exosomes as a highly potent form of therapeutics with excellent safety profiles for treatment of TNBC. Aim 1 will be design, generation, and characterization of engineered exosomes that can potently activate TNBC-specific antitumor immunity. Aim 2 will be creation and evaluation of reprogrammed exosomes that can specifically induce immune responses toward TNBC tumors. Aim 3 will be elucidation of mechanism(s) of action for identified lead immunotherapeutic exosomes. Successful completion of this project will result in a new class of immunotherapeutics with excellent pharmacological properties, leading to rapid translation into clinical applications and a paradigm shift in TNBC therapy.