Immunotherapeutic Exosomes for Triple Negative Breast Cancer
Creators: name: University Of California Office Of The President
Publisher: name: University of California Office of the President
publisherIdentifier: https://ror.org/00dmfq477
publisherIdentifierScheme: ROR
Year: 2024

description: Breast cancer is the most common cancer and the second deadliest cancer in women in the United States. Among breast cancer patients, about 15-20% are diagnosed with triple negative breast cancer (TNBC), which is defined by the lack of expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). Compared with other breast cancer subtypes, TNBC is highly invasive and metastatic and characterized by aggressive clinical course, high relapse rate, and poor overall survival. Metastasis of TNBC makes significant contribution to the failures of treatment in clinic. Given little efficacy for existing therapeutic regimens against a substantial number of patients with metastatic TNBC, novel treatment strategies with significantly enhanced potency and safety are still urgently required to address unmet medical needs. Compared with conventional chemotherapy, therapeutic agents that can effectively activate the immune system for robustly destroying TNBC cells have emerged as increasingly important anti-tumor therapies. However, due to limited efficacy and considerable safety concerns for existing immunotherapies, more efficacious and safer therapeutic regimens are urgently required to address unmet medical needs and advance understanding of anti-tumor immunity for improved control and manipulation of the immune response. Herein, we propose to develop a novel class of therapeutics that can selectively redirect and activate the immune cells against TNBC cells for killing. 
 The question(s) or central hypotheses of the research: The proposed innovative class of therapeutics will be generated through engineering cell-derived nanoparticles. Compared with conventional nanomedicines which prove to be unsafe and lack of effectiveness, these newly designed nanoscale controllers based on naturally occurring nanoparticles are hypothesized to possess the power to control the immune system in a directed manner for more effective and selective attacking of TNBC cells. 
 The general methodology: We creatively combine knowledge and technologies from cell biology, protein engineering, and nanotechnology to engineer cell-derived nanoparticles. The reprogrammed cell-derived nanoparticles will be examined using physical, chemical, and biological approaches to determine their stability and activity for inducing anti-TNBC tumor immunity. Their effectiveness and selectivity will then be further optimized and assessed by performing preclinical studies using animal models bearing tumors derived from human TNBC cells, a critical step for moving toward early stages of clinical trials. 
 Innovative elements of the project and potential impact: Our proposed immunotherapeutics are unique and distinguished from conventional regimens. We introduce a novel concept in generating immunotherapeutic candidates against TNBC and propose to develop for the first time an innovative class of cell-free therapeutics that may have excellent effectiveness and safety profiles. Successful completion of this research project will not only lead to the development of an innovative class of immunotherapeutics for more effective treatment of TNBC, but also a generally applicable and versatile platform technology for production of next-generation immunotherapeutics to combat many other types of cancer. The results from these preclinical studies will demonstrate feasibility and provide a strong basis for subsequent clinical trials. These new therapeutic regimens are expected to provide more efficacious approaches with fewer side effects for TNBC therapies, as well as powerful tools for fighting TNBC with developed drug resistance.