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Early detection of HCC using noninvasive activity-based nanosensors

Award Information
Agency: Department of Health and Human Services
Branch: National Institutes of Health
Contract: 4R44CA228743-02
Agency Tracking Number: R44CA228743
Amount: $1,983,597.00
Phase: Phase II
Program: SBIR
Solicitation Topic Code: 102
Solicitation Number: PA18-574
Solicitation Year: 2018
Award Year: 2020
Award Start Date (Proposal Award Date): 2020-08-20
Award End Date (Contract End Date): 2022-07-31
Small Business Information
Cambridge, MA 02139-3543
United States
DUNS: 080358594
HUBZone Owned: No
Woman Owned: Yes
Socially and Economically Disadvantaged: No
Principal Investigator
 (617) 710-8781
Business Contact
Phone: (408) 306-9331
Research Institution

Project Summary/Abstract
Hepatocellular carcinoma (HCC) is the most common primary liver cancer and arises from chronic liver
diseases (CLD) including hepatitis B virus (HBV), hepatitis C virus (HCV), alcoholic liver disease (ALD), and
nonalcoholic steatohepatitis (NASH). Today, patients with CLDs are at high risk for HCC and are monitored
closely by imaging and serum biomarkers, but these platforms lack sensitivity for early stage HCC.
Consequently, although HCC can be cured by surgical resection, less than 10% of the greater than 500,000
newly diagnosed HCC patients per year worldwide undergo surgical resection because of late diagnosis. This
proposal aims to develop the Glympse liver test (GLT), a multiplexed, injectable diagnostic of activity-based
probes, which detect the activity of proteases that drive the pathological hallmarks of early stage HCC. These
HCC-specific proteases are upregulated regardless of etiology and their activities drive fundamental tumor
processes including angiogenesis, inflammation, and ECM degradation. The GLT platform is ultrasensitive to
early stage HCC by relying on two mechanisms for signal amplification; detection signals are generated by
protease activity which amplifies signals by enzyme turnover, and are concentrated by renal filtration into urine
for quantification by mass spectrometry. We will identify etiology independent HCC proteases and formulate
GLT nanosensors on inert polymer scaffolds for human use. We will then validate the ability of GLT to detect
early stage HCC in mouse models covering major etiologies, benchmarking against imaging and serum
biomarkers, and then conduct preclinical toxicology studies in preparation for an IND submission. The GLT
offers clinician a rapid and sensitive diagnosis of early stage HCC compared to imaging and blood biomarkers.
The ability of GLT to detect HCC at an early stage will significantly improve response rates (60–70% at Stage
1), saving 20,000 lives from 30,000 patient deaths every year. The benefit to the healthcare system will be
greater than $400 million based on increasing the number of curative resection surgeries while significantly
reducing the number of liver transplants. The impact of the GLT for HCC will increase early stage diagnosis
rates, reduce healthcare costs associated with treating late-stage HCC, and ultimately improve patient
outcomes due to increased treatment options for physicians.Project Narrative
Hepatocellular carcinoma (HCC) arises from many different chronic liver diseases and if detected early, patients
can be cured by surgery. However, current diagnostic platforms including imaging and blood biomarkers are not
sensitive for early stage disease. This project aims to develop an ultrasensitive urine diagnostic to detect early
stage HCC to significantly increase patient response and cure rates to therapy.

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

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