Reprogramming Exosomes for Novel Immunotherapy of Triple Negative Breast Cancer

摘要 三阴性乳腺癌（TNBC）占乳腺癌的约15-20%，并且是最常见的乳腺癌。 乳腺癌的侵袭性亚型鉴于现有的治疗方案对显著的 TNBC患者的数量和TNBC细胞对化疗的持续耐药性，新的 仍然迫切需要具有显著增强的效力和安全性的治疗策略来解决未满足的问题， 医疗需求。外泌体是由许多类型的细胞分泌的天然膜囊泡，并且具有许多生物学特性。 药物开发的重要和宝贵的功能。通过利用这些独特的生物和 外泌体的药理学特性，我们的目标是开发创新的合成外泌体作为一种高度 具有优异的安全性特征的有效形式的治疗剂用于治疗TNBC。目标1将是设计，生成， 和表征可以有效激活TNBC特异性抗肿瘤免疫的工程化外泌体。目的 2将创建和评估可以特异性诱导免疫反应的重编程外泌体 TNBC肿瘤目的3是阐明已确定的铅免疫抑制剂的作用机制 外来体该项目的成功完成将导致一类新的免疫治疗药物， 药理学特性，导致快速转化为临床应用和TNBC的范式转变 疗法

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.