Engineered platelets for the targeted destruction of circulating tumor cells - Administrative Supplement

用于定向破坏循环肿瘤细胞的工程血小板 - 行政补充

• 批准号: 10599722
• 负责人: Tara Lynn Deans
• 金额: $ 6.81万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-20 至 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10599722
• 关键词: Administrative Supplement; Apoptosis; Blood Circulation; Blood Platelets; Cancer Etiology; Cell Therapy; Development; Disease; Distant; Engineering; Extracellular Matrix; Face; Goals; Health; Human; Immunologic Surveillance; Immunologics; Invaded; Location; Malignant Neoplasms; Methods; Neoplasm Circulating Cells; Neoplasm Metastasis; Organ; Patients; Primary Neoplasm; Prognosis; Site; Survival Rate; Therapeutic; Tissues; cancer cell; cancer therapy; circulating cancer cell; delivery vehicle; improved; mortality; next generation; novel; prevent; small molecule; trafficking; tumor

Project summary The goal of this proposal is to increase our understanding of the therapeutic benefits of using platelets for preventing the spread of cancer, or metastasis. Metastasis is the main cause of cancer-associated mortality that occurs when some cancer cells, also called circulating tumor cells (CTCs), detach from primary tumor sites and enter the bloodstream to invade other tissues and organs at different locations. The presence of CTCs in patients is associated with a poor prognosis because once CTCs enter the bloodstream it is difficult to prevent them from reaching secondary organs and spreading cancer. Therefore, targeting CTCs may represent a promising target for anticancer therapies. Once CTCs enter into the bloodstream, they face many survival challenges including immunological attack, shear forces, and apoptosis. To enhance their survival rate, CTCs strongly attract platelets to form a protective cloak that helps the cancer cells survive the forces in the bloodstream and to escape immune surveillance. Although the mechanisms by which platelets interact with circulating tumor cells are poorly understood, studies have shown that they are involved in cancer progress, especially during metastasis where platelets help to degrade extracellular matrix (ECM) to support the colonization of cancer cells in distant locations from the original tumor formation site. We propose to take advantage of platelets' innate association with circulating tumor cells and their storage, trafficking, and release capacities of small molecules, to engineer them as delivery vehicles for the development of next generation delivery methods for targeting and destroying CTCs to prevent or minimize metastasis.

项目摘要 该建议的目的是增加我们对使用血小板的治疗益处的理解 防止癌症或转移的传播。转移是癌症相关死亡率的主要原因 当一些癌细胞（也称为循环肿瘤细胞（CTC））脱离原发性肿瘤时发生的 位置并进入血液，以在不同位置侵入其他组织和器官。存在 患者的CTC与预后不良有关，因为一旦CTC进入血液，很难很难 防止它们到达次要器官并扩散癌症。因此，针对CTC可能 代表了抗癌疗法的有希望的靶标。 一旦CTC进入血液，他们将面临许多生存挑战，包括免疫攻击， 剪切力和凋亡。为了提高其存活率，CTC强烈吸引血小板形成保护性 帮助癌细胞在血液中生存并避免免疫监测的斗篷。 尽管对血小板与循环肿瘤细胞相互作用的机制知之甚少，但研究 已经表明它们参与了癌症的进展，尤其是在血小板有助于的转移中 降解细胞外基质（ECM），以支持远距离位置的癌细​​胞的定殖 原始肿瘤形成部位。我们建议利用血小板与循环的天生联系 肿瘤细胞及其存储，运输和释放小分子的能力，以设计它们 用于开发下一代递送方法的运输车辆，用于靶向和破坏CTC 预防或最小化转移。