CTC Screening Assay to Address Health Disparities in Women with Ovarian Cancer

 描述(申请人提供)：卵巢上皮癌(EOC)是美国女性癌症相关死亡的第五大原因，也是妇科癌症的头号杀手，2014年报告了约22,000例病例。EoC一直被称为“沉默的杀手”，因为大多数女性(70%)是在疾病晚期被诊断出来的，这是因为缺乏临床上敏感和特异的筛查测试，而且在疾病发生晚期之前没有症状。虽然美国的EOC发病率在白人女性中最高，但在其他人群中，诊断后的结果存在显著差异，根据5年存活率，非裔美国女性的死亡率要高得多。早期发现战略不足以及手术治疗机会减少(在疾病后期需要)似乎是造成这种差异的原因之一。因此，迫切需要改善获得先进筛查分析的机会，从而更早地发现，以改善结果，特别是在受不同影响的人群中。对癌症患者血液中循环肿瘤细胞(CTC)的分析已经证明了对转移性癌症的预后价值[1](1)(1)(1)，但使用CTC诊断早期疾病需要一定程度的敏感性和特异性，这在现有的CTC分析技术中是无法实现的。这项SBIR研究项目将产生一种创新的CTC检测技术，该技术将具有独特的能力，适用于EOC和潜在的其他癌症的早期检测。该技术使用低成本的一次性塑料CTC流控色谱柱，能够以极高的回收率(&gt；90%)、前所未有的纯度(&gt；85%)直接从全血中选择CTCs，并可以使用简单的单细胞传感器(Micro-CTC Coulter Counter，µC3)使用无标记方法来计数捕获的CTCs。该技术提供了具有全流程自动化的简单工作流程，非常适合在资源有限的环境中使用的筛查测试。该技术将直接处理全血(约2毫升输入)，并亲和选择CTCs，从捕获表面释放CTCs，并使用芯片上的µC3进行计数。我们平台的独特之处在于能够从单个样本中选择不同的CTCs亚群。BioFluidica已经使用一种新型的CTC分离抗原测试了其捕获系统，初步数据表明，与更常用的选择靶点上皮细胞黏附分子(EpCAM)相比，这种抗原在早期疾病中更常见。捕捉多个阶段特定的CTC亚群的能力有可能在疾病的早期阶段诊断患者，以及评估治疗效果和疾病复发的可能性。这项提议的目标是启动一种强大的EOC筛查测试的开发，加快治疗并改善目前不良的预后，特别是在受不同影响的非裔美国妇女中。这一第一阶段计划的成功完成将推动该技术进入对其他表现出差异的癌症的早期检测场景，例如非裔美国女性的乳腺癌。

 DESCRIPTION (provided by applicant): Epithelial Ovarian Cancer (EOC) is the 5th leading cause of cancer-related deaths among women in the US and is the leading gynecological cancer killer with ~22,000 cases reported in 2014. EOC has been called a "silent killer" because most women (>70%) are diagnosed at late stages of disease due to a lack of clinically sensitive and specific screening test and a lack of symptoms until late stage disease onset. While the incidence rate of EOC in the US is highest among white females, there exists a dramatic disparity in post-diagnosis outcomes in other populations with African-American women exhibiting substantially greater mortality based on 5-year survival rates. A combination of insufficient early detection strategies as well as reduced access to surgical treatment (required at later stages of disease) appears to contribute to the disparity. Improved access to advanced screening assays, and thereby earlier detection, is therefore urgently needed to improve outcomes, particularly in disparately effected populations. Analysis of circulating tumor cells (CTCs) from cancer patients' blood have demonstrated prognostic value in metastatic cancers (1) (1)(1)but the use of CTCs for diagnosing early stage disease requires a degree of sensitivity and specificity currently unavailable in existing CTC analysis technologies. An innovative CTC detection technology will emanate from this SBIR research project that will have unique capabilities suited to the early detection of EOC and potentially other cancers as well. The technology uses low-cost, disposable, plastic CTC fluidic cartridge that possess the ability to select CTCs directly from whole blood with extremely high recoveries (>90%), unprecedented purities (>85%) and can enumerate the captured CTCs using a label-less approach with a simple single-cell transducer (micro-CTC Coulter Counter, µC3). The technology provides a simple workflow with full process automation, ideal for a screening test that can be utilized within resource-limited settings. The technology will process whole blood directly (~2 mL input) and affinity select the CTCs, release the CTCs from the capture surface and count them using an on-chip µC3. Unique to our platform is the ability to select different CTCs subpopulations from a single sample. BioFluidica has tested its capture system using a novel CTC-isolation antigen, which, as the preliminary data indicates, is more prevalent in early stage disease compared to the more commonly used selection target, epithelial cell adhesion molecule (EpCAM). The ability to capture multiple stage-specific CTC subpopulations has the potential to diagnose patients at early stages of disease as well as assess treatment efficacy and the potential for disease recurrence. The goal of this proposal is to initiate the development of a powerful EOC screening test, accelerating treatment and improving currently poor prognoses, especially in disparately affected African-American women. Successful completion of this Phase I program will provide the impetus to move the technology into early detection scenarios for other cancers that show disparities, such as breast cancer in African-American women.