Reprogramming Exosomes for Novel Immunotherapy of Triple Negative Breast Cancer

重编程外泌体用于三阴性乳腺癌的新型免疫疗法

• 批准号: 10733734
• 负责人: Yong Zhang
• 金额: $ 51.18万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-04 至 2028-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10733734
• 关键词: Address; Affinity; Antibodies; Binding; Biological; Biology; Blood specimen; Breast Cancer Cell; Breast Cancer Patient; Breast Cancer cell line; Breast Cancer therapy; CD3 Antigens; Cell Line; Cellular Immunity; Cytotoxic T-Lymphocytes; Development; Dioxygenases; Effector Cell; Encapsulated; Epidermal Growth Factor Receptor; ErbB Receptor Family Protein; Evaluation; Extracellular Domain; Fostering; Generations; Goals; Human; Immune; Immune response; Immunosuppression; Immunotherapeutic agent; Immunotherapy; Implant; In Vitro; Lead; Ligands; Link; Mediating; Medical; Membrane Proteins; Monoclonal Antibodies; Mus; Nanotechnology; Organ; Pathway interactions; Patients; Peripheral Blood Mononuclear Cell; Property; Protein Engineering; Pyrroles; Receptor Protein-Tyrosine Kinases; Regimen; Resistance development; Safety; Sampling; Specificity; Surface; T-Lymphocyte; Therapeutic; Toxic effect; Translations; Tumor Immunity; Tumor-Derived; Vesicle; anti-cancer; antibody immunotherapy; cancer immunotherapy; cell type; chemotherapy; clinical application; cytotoxic; cytotoxicity; design; drug development; effective therapy; engineered exosomes; exosome; humanized mouse; immune checkpoint; immunological synapse formation; immunoreactivity; improved; in vivo; indoleamine; inhibitor; innovation; insight; malignant breast neoplasm; novel; novel therapeutics; overexpression; pharmacologic; polypeptide; programmed cell death ligand 1; programmed cell death protein 1; receptor; targeted delivery; therapeutic candidate; treatment strategy; triple-negative invasive breast carcinoma; tumor; tumor necrosis factor ligand superfamily member 4

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.

摘要