Publications

Improving the future of early cancer detection through rigorous science.

Colocalization of ovarian cancer-associated biomarkers in tumors, cancer cells and extracellular vesicles

OVARIAN CANCER

2024 American Association for Cancer Research (AACR) Annual Meeting

We have previously shown that ovarian cancer can be detected by interrogating colocalized, membrane-associated cell-surface biomarkers on single extracellular vesicles (EVs). Our blood-based Ovarian Cancer Test (OC Test) detects cancer-associated EVs from human plasma to distinguish high-grade serous ovarian carcinoma (HGSC) from both benign ovarian tumors and normal samples. Using nanoimaging of human cell line EVs and mIHC staining of ovarian benign and tumor tissue, we show that the ovarian cancer biomarkers detected by our assay demonstrate colocalization on the surface EVs and on cancer cells within ovarian tumor biopsies, and that expression and colocalization of the biomarkers correlates with assay signal from patient plasma samples.  The results demonstrate that the OC Test biomarkers are both enriched and colocalized on tumor tissue and EVs from ovarian cancer cell lines. These results provide further evidence that colocalized biomarkers on EVs can be utilized for the early detection of HGSC.

Improving specificity for ovarian cancer screening using a novel extracellular vesicle-based blood test

OVARIAN CANCER

2023 AACR Special Conference in Cancer Research: Ovarian Cancer

There are currently no recommended screening methods for ovarian cancer, therefore new diagnostic methods that can detect the disease at early stages when clinical intervention is most effective are needed. The low incidence of ovarian cancer (OC) in average risk individuals dictates any OC screening method needs to be both highly sensitive and highly specific. In the UKCTOCS study using a multimodal OC screening strategy combining longitudinal serum CA125 and transvaginal ultrasound, 16% of OCs were not detected and false positives due to benign ovarian tumors, which are 5-10 times more prevalent than OC, remained high. Due to lack of mortality benefit for current screening methods, population screening is not recommended. We hypothesized
that detecting multiple membrane surface associated biomarkers on single tumor associated extracellular vesicles (EVs) would increase specificity and sensitivity for detection of OC.

Development and characterization of a liquid biopsy assay for the detection of colocalized biomarkers on extracellular particles

OVARIAN CANCER

2023 International Society for Extracellular Vesicles

Detection of early-stage cancer, when it is most treatable, remains a significant challenge. Extracellular particles (EPs) derived from cancer cells offer a unique analyte for diagnostic tests given their abundance, stability, and representation of the cell of origin. Here, we describe the development of Mercy Halo™, an immunoassay designed to capture and detect up to three distinct, colocalized biomarkers on tumor-derived EPs in human blood samples. In proof-of-concept testing, we demonstrate the sensitive and specific detection of stage I and II high-grade serous ovarian cancer (HGSOC) in human plasma, outperforming CA125 in the discrimination of benign and malignant ovarian masses.

Colocalization of cancer-associated biomarkers on single extracellular vesicles for early-cancer detection

OVARIAN CANCER

2023 American Association of Cancer Research (AACR) Annual Meeting

Tumor-derived extracellular vesicles (TDEVs) are an ideal analyte for liquid biopsy diagnostic assays. We describe a platform technology, Mercy Halo™, which interrogates millions of individual EVs within a plasma or serum sample to capture and detect TDEVs.  We demonstrate that biomarkers present on cancer cells are colocalized on EVs derived from a tumor and are readily detectable using the Mercy Halo platform. Using panels of antibodies targeting up to three cancer-associated biomarkers simultaneously, we demonstrate Mercy Halo enables sensitive and specific detection of early-stage high-grade serous ovarian carcinoma (HGSOC) with excellent reproducibility in a proof-of-concept (PoC) study.

Development and preliminary validation of a test for early-stage cancer detection measuring colocalized biomarkers on single extracellular vesicles

OVARIAN CANCER AND LUNG CANCER

2022 Early Detection of Cancer Conference

Colocalization of cancer-associated biomarkers on intact, single extracellular vesicles (EVs) is a novel approach that can dramatically boost early-stage sensitivity of a liquid biopsy test. To leverage this principle, we developed Mercy Halo™—a platform technology that detects tumor-derived EVs in blood displaying multiple colocalized cancer-associated biomarkers. We
assessed the clinical feasibility of this approach by applying the technology to early-stage ovarian cancer (OC) and lung cancer (LC) detection.

Extracellular vesicle-based biomarker assay for the detection of early-stage ovarian cancer

OVARIAN CANCER

2022 American Society of Clinical Oncology (ASCO) Annual Meeting 

Detection of cancer with improved discrimination compared to current blood tests could be achieved using an approach that assesses extracellular vesicles (EVs). This approach should have high sensitivity (se) because of EVs abundance in blood and high specificity (sp) by assaying EVs with multiple cancer-related protein and glycosylation epitopes (PGEs) co-localized on their surfaces. We are developing a platform technology that detects multiple cancer-related PGEs co-localized on the same EV using immunoaffinity-capture and proximity-ligation qPCR. In this study, we compare the performance of this technology vs plasma CA125 for correctly categorizing early-stage high-grade serous ovarian cancer (HGSOC) vs healthy/benign ovarian tumors (OT).

Preliminary results for a novel single extracellular vesicle assay for early-stage ovarian cancer: The power of co-localized detection of surface biomarkers

OVARIAN CANCER

2022 American Association for Cancer Research (AACR) Annual Meeting

 

These preliminary data suggest that co-localization of surface biomarkers in single EVs may provide an effective means to identify women with early-stage high-grade serous ovarian cancer (HGSOC), including those with normal CA125, while avoiding false positives in women with benign masses and high CA125. Despite the inherent challenges associated with commercial samples, our finding that several combinations detected early-stage HGSOC is promising. Statistically powered studies with curated repository specimens are underway to refine combinations and independently validate our assay for early-stage ovarian cancer detection.

Preliminary results for a novel single extracellular vesicle assay for early lung cancer: The power of co-localized detection of surface biomarkers

LUNG CANCER

2022 American Association for Cancer Research (AACR) Annual Meeting

These preliminary data highlight the potential of detecting biomarkers co-localized on the surface of single EVs as an effective tool for early-stage lung cancer detection, and the benefit of using 3 biomarkers simultaneously. Despite inherent challenges associated with commercial samples, our finding that detection of co-localized EV surface biomarkers distinguished lung adenocarcinoma (LUAD) is promising. Additional studies with lung cancer cohorts beyond LUAD are underway to refine combinations and independently validate our assay for early-stage lung cancer detection.