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

CTC 筛查测定可解决卵巢癌女性的健康差异

• 批准号: 9000971
• 负责人: Mateusz Lukasz Hupert
• 金额: $ 19.98万
• 依托单位: BIOFLUIDICA, INC
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-17 至 2017-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9000971
• 关键词: Address; Affect; Affinity; African American; Antibodies; Antigens; Automation; Biochemical; Biological Assay; Blood; Blood specimen; Cancer Etiology; Cancer Patient; Caring; Case Study; Cell Adhesion Molecules; Cell Separation; Cells; Cessation of life; Collaborations; Coulter counter; Cytokeratin; Data; Data Reporting; Detection; Development; Diagnosis; Diagnostic; Disease; Disseminated Malignant Neoplasm; Early Diagnosis; Electrodes; Epidemiology; Epithelial; Epithelial Cells; Epithelial ovarian cancer; Ethnic group; Exhibits; Female; Genetically Engineered Mouse; Goals; Image; Immobilization; Immunophenotyping; Improve Access; Incidence; Label; Leukocytes; Malignant Female Reproductive System Neoplasm; Malignant Neoplasms; Malignant neoplasm of ovary; Methods; Microfluidics; Modality; Modeling; Molds; Neoplasm Circulating Cells; Onset of illness; Operative Surgical Procedures; Optics; Outcome; PTPRC gene; Patients; Peptides; Peripheral; Phase; Plastics; Population; Printing; Process; Recovery; Recurrence; Research Project Grants; Resources; Sampling; Sensitivity and Specificity; Small Business Innovation Research Grant; Staging; Surface; Survival Rate; Symptoms; System; Techniques; Technology; Temperature; Testing; TimeLine; Transducers; Treatment Efficacy; Validation; Whole Blood; Woman; base; cancer health disparity; chemotherapy; cost; cost effective; design; experience; health disparity; improved; innovation; innovative technologies; instrumentation; malignant breast neoplasm; medical schools; mortality; mouse model; new technology; novel; outcome forecast; peripheral blood; prognostic value; programs; public health relevance; response; screening; standard of care; treatment response; tumor

 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.

 描述（由申请人提供）：上皮性卵巢癌 (EOC) 是美国女性癌症相关死亡的第五大原因，也是主要的妇科癌症杀手，2014 年报告了约 22,000 例病例。EOC 被称为“沉默的杀手”，因为大多数女性 (>70%) 在疾病晚期被诊断出来，因为缺乏临床敏感和特异性的筛查测试，并且直到疾病晚期才出现症状。虽然美国 EOC 的发病率在白人女性中最高，但其他人群的诊断后结果存在巨大差异，根据 5 年生存率，非裔美国女性的死亡率要高得多。早期检测策略不足以及手术治疗（疾病后期所需）的机会减少似乎导致了这种差异。因此，迫切需要改善先进筛查分析的获取，从而实现更早检测，以改善结果，特别是在不同受影响的人群中。对癌症患者血液中的循环肿瘤细胞 (CTC) 的分析已证明对转移性癌症具有预后价值 (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，而现有的 CTC 分析技术目前无法实现。该 SBIR 研究项目将产生一种创新的 CTC 检测技术，该技术将具有适合早期检测 EOC 和其他潜在癌症的独特功能。该技术使用低成本、一次性塑料 CTC 流体盒，能够直接从全血中选择 CTC，具有极高的回收率 (>90%)、前所未有的纯度 (>85%)，并且可以使用无标记方法和简单的单细胞传感器（微型 CTC Coulter 计数器，μC3）对捕获的 CTC 进行计数。该技术提供了一个简单的工作流程和完整的过程自动化，非常适合在资源有限的环境中使用的筛选测试。该技术将直接处理全血（约 2 mL 输入）并亲和选择 CTC，从捕获表面释放 CTC，并使用片上 µC3 对它们进行计数。我们平台的独特之处在于能够从单个样本中选择不同的 CTC 亚群。 BioFluidica 已使用一种新型 CTC 分离抗原测试了其捕获系统，正如初步数据所示，与更常用的选择目标上皮细胞粘附分子 (EpCAM) 相比，该抗原在早期疾病中更为普遍。捕获多个阶段特异性 CTC 亚群的能力有可能在疾病早期诊断患者，并评估治疗效果和疾病复发的可能性。该提案的目标是启动强大的 EOC 筛查测试的开发，加速治疗并改善目前较差的预后，特别是对于受影响不同的非裔美国女性。第一阶段计划的成功完成将推动该技术进入其他存在差异的癌症的早期检测场景，例如非裔美国女性的乳腺癌。