Renal Cell Carcinoma Surveillance by Immuno-Lipoplex Nanoparticle Platform

通过免疫脂质体纳米颗粒平台监测肾细胞癌

• 批准号: 10544876
• 负责人: Wen Jiang
• 金额: $ 19.15万
• 依托单位: UNIVERSITY OF TX MD ANDERSON CAN CTR
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-06-01 至 2023-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10544876
• 关键词: Renal; Cell; Carcinoma; Surveillance; Immuno

Project Summary Kidney cancer is a common and deadly malignancy, with more than 73,000 new cases and 14,000 deaths estimated to occur in 2019 in the United States. Renal cell carcinoma (RCC) is the most prevalent type, accounting for more than 90% of all kidney cancers. Surgical resection is the treatment choice for localized RCC, however, patients with RCC are often deemed unfit for surgery because of multiple comorbidities. Stereotactic body radiotherapy (SBRT), characterized by the delivery of high doses of ionizing radiation in a few fractions, can overcome the radioresistance of RCC and achieve high therapeutic efficiency. Therefore, SBRT is currently considered as an alternative treatment option to manage non-operable patients. Post-treatment surveillance, established on the belief that detecting asymptomatic disease recurrence offers an optimal opportunity for beneficial intervention, is an integral part of RCC care. However, detecting RCC biomarkers by conventional methods requires large sample volumes and tedious work. No molecular biomarkers have been reliably validated or integrated into daily clinical practice to rationally guide kidney cancer therapy after SBRT. Thus, identifying potential RCC post-treatment biomarkers after irradiation with minimum sample preparation and high sensitivity would be invaluable. Recently, ‘liquid biopsy’ relying on detecting circulating tumor cells (CTCs), circulating transcripts, RNAs (miRNAs/mRNAs), and tumor-related genes has been investigated as a potential diagnostic and prognostic biomarker for various cancers. Extracellular vesicles (EVs) such as exosomes are difficult to detect and all current approaches to detect EVs have proven to be tedious, expensive, and time consuming. The primary objective of this R21 proposal is to develop and evaluate a newly developed immune-tethered lipoplex nanoparticle (ILN) technology system for preclinical molecular diagnosis. ILNs are designed to provide a simple, non-invasive, and low-cost method for RCC surveillance after SBRT. To achieve this goal, we have developed a biochip with nanoparticles containing specific molecular beacons (MBs) inside and RCC-specific antibody on the surface. The antibodies can capture EVs with specific RCC surface receptors, and then MBs can bind to the target EV RNAs to produce fluorescence that can be recorded by total internal reflection fluorescence microscope (TIRF). This new biochip allows capturing homogeneous EV subgroups secreted from RCC tumor cells, and measuring both EV RNA and membrane protein targets in a single step. If successfully implemented, this diagnostic and surveillance tool, could be highly transformative for the surveillance of patients with cancer.

项目概要 肾癌是一种常见且致命的恶性肿瘤，有超过 73,000 例新发病例和 14,000 例死亡 估计 2019 年在美国发生的肾细胞癌 (RCC) 是最常见的类型， 占所有肾癌的 90% 以上，手术切除是局限性肾细胞癌的治疗选择。 然而，由于多种立体定向疾病，肾细胞癌患者通常被认为不适合手术。 身体放射治疗（SBRT），其特点是分几次提供高剂量的电离辐射， 可以克服RCC的放射抗性，达到较高的治疗效率。 被认为是管理不可手术患者的替代治疗选择， 建立的信念是检测无症状疾病复发为治疗提供了最佳机会 有益的干预是 RCC 护理的一个组成部分，但是，通过传统方法检测 RCC 生物标志物。 方法需要大量样本和繁琐的工作，目前还没有可靠地验证分子生物标志物。 或纳入日常临床实践，以合理指导 SBRT 后的肾癌治疗，从而确定。 辐射后潜在的肾细胞癌治疗后生物标志物，样品制备最少，灵敏度高 最近，依靠检测循环肿瘤细胞（CTC）的“液体活检”将变得非常有价值。 转录本、RNA (miRNA/mRNA) 和肿瘤相关基因已被研究作为潜在的诊断手段 和各种癌症的预后生物标志物很难确定。 事实证明，目前所有检测电动汽车的方法都是乏味、昂贵且耗时的。 R21提案的主要目标是开发和评估新开发的免疫束缚脂质复合物 用于临床前分子诊断的纳米颗粒 (ILN) 技术系统旨在提供简单、简单的诊断。 为了实现这一目标，我们开发了 SBRT 后的非侵入性且低成本的 RCC 监测方法。 一种生物芯片，其内部含有特定分子信标 (MB) 的纳米粒子，表面带有 RCC 特异性抗体 抗体可以捕获具有特定 RCC 表面受体的 EV，然后 MB 可以与该表面结合。 靶向 EV RNA 产生可通过全内反射荧光记录的荧光 这种新型生物芯片可以捕获 RCC 肿瘤分泌的同质 EV 亚群。 如果成功实施，可以一步测量 EV RNA 和膜蛋白目标。 这种诊断和监测工具可能会对癌症患者的监测产生巨大的变革。