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Developing and Automating an Extracellular Vesicle-Based Test for Early Detection of Hepatocellular Carcinoma

Award Information
Agency: Department of Health and Human Services
Branch: National Institutes of Health
Contract: 1R44CA288163-01
Agency Tracking Number: R44CA288163
Amount: $661,609.00
Phase: Phase II
Program: SBIR
Solicitation Topic Code: 102
Solicitation Number: PA22-176
Solicitation Year: 2022
Award Year: 2023
Award Start Date (Proposal Award Date): 2023-09-14
Award End Date (Contract End Date): 2026-08-31
Small Business Information
Los Angeles, CA 90025-4877
United States
HUBZone Owned: No
Woman Owned: No
Socially and Economically Disadvantaged: No
Principal Investigator
 (310) 794-1977
Business Contact
Phone: (310) 592-5071
Research Institution

Hepatocellular carcinoma (HCC) comprises 80-85% of primary liver cancers and frequently develops in patients
with liver cirrhosis or chronic hepatitis B virus infection. HCC's poor prognosis is primarily due to advanced-stage
diagnosis. Current clinical practice guidelines recommend biannual liver ultrasounds, with or without serum
alpha-fetoprotein (AFP) testing, for at-risk patients to detect HCC at a curable stage. However, their accuracy is
limited, with sensitivity between 60-70% and specificity of 90%. Consequently, novel biomarkers for early
detection of HCC are urgently needed. Extracellular vesicles (EVs) are a heterogeneous group of lipid
nanoparticles that are released by all types of cells, and even more so by tumor cells. Tumor-derived EVs are
present in circulation at relatively early stages of disease and are readily accessible across all disease stages.
Since the surface proteins of tumor EVs mirror those of the parental tumor cells and those cells within tumor
microenvironment, exploiting the diagnostic potential of HCC EVs’ surface protein signatures as a novel
biomarker for early detection of HCC holds great promise to significantly augment the ability of current diagnostic
Over the last five years, our joint team comprised of Eximius Dx, UCLA, and Cedars Sinai Medical Center
(CSMC) has demonstrated of HCC EV Surface Protein (SP) Test, capable of dissecting and quantifying
subpopulations of HCC EVs in plasma samples. In our 2022 Hepatology paper, we summarized a phase-2
biomarker study which successfully validated the feasibility of HCC EV SP Test for early HCC detection. The
long-term goal of this Direct-to-Phase-II proposal is to advance the development, optimization, and automation
of the HCC EV SP Test, with the ultimate goal of establishing a more sensitive in vitro diagnostic (IVD) test based
on HCC EVs. The innovation of the proposed HCC EV SP Test lies in the integration of two platform technologies:
(i) EV Click MagBeads for click chemistry-mediated capture of subpopulations of HCC EVs, and (ii) real-time
immuno-PCR for quantifying the captured HCC EVs. In parallel, an algorithm will be established to process the
resulting HCC EV signatures into HCC EV SP score for distinguishing early-stage HCC from at-risk cirrhosis.
This new IVD test will use less then 1-mL plasma and have a sample-to-answer workflow of no more than 3
hours. By adopting an in-house developed robotic system, the automated workflow allows for a throughput rt
480 samples per round. Once optimized and automated the HCC EV SP Test will be validated by clinically
annotated plasma samples to assess its diagnostic performance for distinguishing early-stage HCC from at-risk
liver cirrhotic patients, covering etiologies including alcohol-associated liver disease (ALD), non-alcoholic fatty
liver disease (NAFLD), and viral hepatitis (B/C). The successful development of the proposed HCC EV SP Test
is rapidly translatable, enabling a sensitive HCC EV-based IVD test for detecting early-stage HCC.

* Information listed above is at the time of submission. *

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