Non Invasive Treatment Response Monitoring and molecular characterization of NSCLC using Cell-free DNA isolated by an AC Electrokinetic Device

使用交流电动装置分离的游离 DNA 对 NSCLC 进行非侵入性治疗反应监测和分子表征

• 批准号: 9067739
• 负责人: PAUL J GRIPPO
• 金额: $ 9.3万
• 依托单位: UNIVERSITY OF ILLINOIS AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-07-23 至 2017-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9067739
• 关键词: Adult; Agreement; American; Biological; Biological Assay; Biological Markers; Blood; Blood specimen; Cancer Patient; Cessation of life; Clinical; DNA; Data; Development; Device or Instrument Development; Devices; Diagnosis; Fluorescence; Future; Goals; Health; Image; Incidence; Knowledge; Lead; Light Exercise; Malignant Neoplasms; Malignant neoplasm of lung; Measurement; Methods; Mind; Molecular; Molecular Profiling; Monitor; Non-Small-Cell Lung Carcinoma; Outcome; Patients; Phase; Physicians; Plasma; Radiation; Reproducibility; Research; Sampling; Scanning; System; Technology; Therapeutic Agents; Time; Variant; Whole Blood; cancer imaging; cancer therapy; cell free DNA; charge coupled device camera; clinical care; commercialization; cost; cost effective; fluorescence microscope; health care quality; human study; improved; monitoring device; mortality; outcome forecast; personalized medicine; phase 2 study; point of care; prototype; response; tool; treatment response; tumor; volunteer

DESCRIPTION (provided by applicant): Our overall goal is to commercialize a cost effective, rapid, point-of-care, treatment response monitoring system that can identify non-responding patients with non-small cell lung cancer (NSCLC) that would be vital to doctors who determine the course of therapy. In this Phase I proposal, we will demonstrate that an inexpensive prototype AC electrokinetic (ACE) Chip developed at Biological Dynamics, Inc. can effectively isolate cell-free circulating DNA directly from plasma rapidly, and establish the proof of concept for using CFC DNA quantitation as a molecular signature for treatment response monitoring (TRM). Lung Cancer is the most common human adult cancer in terms of both incidence and mortality. In 2008, there were 1.61 million new cases, and 1.38 million deaths due to lung cancer worldwide. Prognosis is generally very poor: of all people with lung cancer, only 15% survive for five years after diagnosis. The standard method of monitoring of response to therapy is serial imaging done every 2-3 months. In the research setting, RECIST criteria are used to define progression, but in the regular practice setting, nearly any increase in tumor size can be called progression and initiate change in therapy. Therefore, by the time progression is identified on the imaging, the tumor has been progressing for the previous 2-3 months without knowledge of treating physician. More frequent imaging raises the cost of clinical care and exposes patient to unnecessary radiation. Cell-free DNA in both plasma and serum has been found to be a good marker in lung cancer to evaluate response to therapy immediately after therapy is initiated, and therefore could be used to cause a more immediate change in therapy to improve outcomes. AC Electrokinetic (ACE) isolation and quantification of cell-free circulating DNA (CFC DNA) represents an attractive way to perform treatment response monitoring without increasing the cost. This project will focus on the aspect of using a proprietary ACE device to isolate and analyze CFC DNA from NSCLC patient blood. The specific aims for the Phase I proposal are: 1 - Determine day-to-day variability of ACE results. 2 - In a small human study, determine relationship between radiological estimate of change in tumor size and ACE estimate using blood sample data. A future Phase II proposal will construct an analytical system for commercialization, perform a 100 patient study where non-responders will be identified using the ACE technology and then switch the course of treatment to provide more favorable outcomes to the patient. The Phase II study will also develop a POC assay for FDA submission.

描述（由申请人提供）：我们的总体目标是将一种具有成本效益、快速、即时护理、治疗反应监测系统商业化，该系统可以识别非小细胞肺癌（NSCLC）无反应患者，这对医生决定治疗过程至关重要。在这个第一阶段的提案中，我们将展示由生物动力公司开发的廉价原型交流电动（ACE）芯片可以有效地直接从血浆中快速分离无细胞循环DNA，并建立使用CFC DNA定量作为治疗反应监测（TRM）的分子标记的概念证明。就发病率和死亡率而言，肺癌是最常见的成人癌症。2008年，全世界有161万新病例，138万人死于肺癌。预后通常很差：在所有肺癌患者中，只有15%的人在诊断后能存活5年。监测治疗反应的标准方法是每2-3个月进行一次连续影像学检查。在研究环境中，RECIST标准用于定义进展，但在常规实践环境中，几乎任何肿瘤大小的增加都可以称为进展，并开始改变治疗。因此，在影像学上发现进展时，肿瘤已经进展了2-3个月，而治疗医生并不知情。更频繁的成像增加了临床护理的成本，并使患者暴露在不必要的辐射中。血浆和血清中的无细胞DNA已被发现是肺癌治疗开始后立即评估治疗反应的良好标志物，因此可用于引起治疗的更直接改变以改善结果。交流电动力学（ACE）分离和定量无细胞循环DNA （CFC DNA）是一种有吸引力的方法，可以在不增加成本的情况下进行治疗反应监测。本项目将侧重于使用专有的ACE设备从非小细胞肺癌患者血液中分离和分析CFC DNA。第一阶段建议的具体目标是：1 -确定ACE结果的日常变异性。在一项小型人体研究中，利用血液样本数据确定肿瘤大小变化的放射学估计与ACE估计之间的关系。未来的II期计划将构建一个商业化的分析系统，进行100例患者的研究，使用ACE技术识别无反应者，然后切换治疗过程，为患者提供更有利的结果。II期研究还将开发POC检测，以提交FDA。