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Early Detection through Novel OCEAN Technology - Ovarian Cancer Exosomal Analysis with Nanoplasmonics

通过新型 OCEAN 技术进行早期检测 - 使用纳米等离子体技术进行卵巢癌外泌体分析

基本信息

批准号：
10223236
负责人：
Cesar M Castro
金额：
$ 74.67万
依托单位：
MASSACHUSETTS GENERAL HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-09-01 至 2023-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10223236
关键词：
Address Adopted Adoption Animal Model Ascites Benign Biological Biological Assay Blood Tests Cancer Diagnostics Cancer Patient Carcinoma Cell Culture Techniques Cells Clinical Clinical Research Collection Complex Consumption Culture Media Custom Development Device Designs Diagnostic Early Diagnosis Ensure Enzyme-Linked Immunosorbent Assay Epithelial Cells Epithelial ovarian cancer Excision General Hospitals Genetic Risk Genetically Engineered Mouse Goals Hospitals Human Industry Industry Standard Laboratories Lead Liquid substance Malignant - descriptor Malignant Female Reproductive System Neoplasm Malignant Neoplasms Malignant neoplasm of ovary Mammalian Oviducts Massachusetts Measures Medical Device Membrane Membrane Proteins Methods Microfabrication Modeling Molecular Molecular Analysis Monitor Mutation Nanotechnology Nucleic Acids Oceans Operative Surgical Procedures Outcomes Research Ovarian Ovary Pathogenesis Pathology Patients Performance Perinatal Peritoneal Plasma Preclinical Testing Preparation Protein Analysis Proteins Protocols documentation Quality Control Reader Reproducibility Resources Sampling Sampling Biases Screening for Ovarian Cancer Screening for cancer Serous Signal Transduction Standardization Statistical Data Interpretation System Systems Biology TP53 gene Techniques Technology Testing Thinking Time Translating Translations Tumor Burden Ultracentrifugation Validation Variant Vesicle Western Blotting Woman advanced disease assay development base cancer care cancer cell circulating biomarkers clinical diagnostics clinical translation clinically relevant clinically translatable comparative design early detection biomarkers exosome experience extracellular vesicles high risk population high throughput technology improved in-vitro diagnostics industry partner innovation innovative technologies instrument laboratory equipment liquid biopsy minimally invasive multidisciplinary nanoplasmonic nanoscale next generation novel novel marker particle peripheral blood pre-clinical research preclinical study product development prophylactic prospective research clinical testing screening sensor sensor technology success survivorship tool translational impact tumor heterogeneity tumor progression

项目摘要

Extracellular vesicles (EVs) are a new class of circulating biomarker that promises non-invasive, real-time cancer monitoring. Many studies have shown that i) EVs may function as reliable surrogates of parental cancer cells, and ii) these vesicles can reﬂect global tumor burden, overcoming limitations of tumor heterogeneity and sampling bias. Translating EV analyses into a clinically relevant cancer test, however, is limited by the lack of standardized, practical methods. Conventional assay tools (e.g., ultracentrifugation, Western blotting, ELISA) require large amounts of EVs and extensive processing, making them impractical for clinical workﬂows. Moreover, variations in sample handling and testing protocols often lead to inconsistent and confounding results. The goal of this proposal is to i) address such technical challenges in EV analyses, and ii) rigorously evaluate EVs' clinical value as a novel biomarker for early detection of ovarian cancer. We formed a strategic academic-industry partnership to achieve this goal: Exosome Diagnostics, an industry leader in EV-based cancer diagnostics, offering ready capacity to develop and manufacture in-vitro diagnostic medical devices; and the Center for Systems Biology at the Massachusetts General Hospital, a pioneer in developing novel analytical technologies for EV analyses. These teams will bring their multidisciplinary expertise, innovative technologies and complementary resources to carry out the following translational projects. First, we will advance a standardized EV assay platform. We will adopt our recently developed ExoLution platform to streamline EV collection, and the nPLEX (nano-plasmonic exosome) technology for high-throughput EV protein screening. Our initial study showed that nPLEX achieved >1000-fold higher sensitivity than conventional methods and yet consumed scant sample volumes (0.1 μL). We now seek to advance nPLEX to the instrument level by i) improving its robustness and throughput, and ii) establishing standardized assay protocols. Leveraging the developmental and regulatory expertise of Exosome Diagnostics, the resulting platform will be ready for translation into clinical diagnostic laboratories. Second, we will perform a targeted clinical study, particularly testing whether EVs can be exploited as a biomarker for early detection of ovarian cancer and progression monitoring. Our preclinical study will use patient-derived ovarian cancer cells and novel genetically engineered mouse models to identify EV protein signatures for ovarian cancer. We will next proﬁle circulating EVs from ovarian cancer patients and assess the correlation between tumor burden and EV protein signature. Our study will be designed to ensure assay reliability and reproducibility, thereby delivering clinically translatable EV diagnostics. We will impose stringent quality controls on device design and sample processing, accrue well-annotated patient and control samples, and perform multisite testing. The technical and scientiﬁc outcomes of this research could have a signiﬁcant translational impact in cancer management, establishing a robust, highly speciﬁc liquid biopsy for early detection of ovarian cancer.

细胞外囊泡（EVs）是一种新型的无创、实时的循环生物标志物