A novel diagnostic biomarker for Hepatocellular Carcinoma(HCC)

Period of Performance: 04/01/2015 - 03/31/2016


Phase 2 SBIR

Recipient Firm

Imcare Biotech
Doylestown, PA 18902
Principal Investigator


DESCRIPTION (provided by applicant): Hepatocellular carcinoma (HCC) is usually undetected until its later stages, where the 5-year survival rate for patients is less than 10%. However, the survival rate can be as high as 40% if the cancer is detected early. Unfortunately, early detection of HCC is not possible with any screening tests that are currently available, such as ultrasound or imaging technologies. Alpha-Fetoprotein (AFP), which is currently the diagnostic marker used for HCC screening, is limited by its low specificity and lack of sensitivity Therefore, a method of detecting HCC accurately and/or in its early stages would greatly improve our ability to manage and treat the disease. Background and Objective: We aim to complete the development of HepatoDetect(r), an ELISA-based diagnostic system, which strongly confirmed its ability to identify both early and late stage Hepatocellular Carcinoma (HCC) with high sensitivity and specificity during our phase I study. The HepatoDetect(r) diagnostic kit is based on the use of a monoclonal antibody to quantitatively detect a protein specifically secreted by liver cancer cells - Liver Cancer-Serine Protease Inhibitor Kazal (LC-SPIK). The effectiveness of LC-SPIK as a marker in distinguishing HCC from other liver diseases, non-liver diseases and healthy subjects was evaluated in phase I and showed that the mean level of LC-SPIK in HCC patients (43ng/ml) was significantly higher (P <0.001) than in patients with hepatitis, liver cirrhosis, pancreatitis and in healthy subjects (11ng/ml, 10ng/ml, 2.3ng/ml and 3.2ng/ml, respectively). Using a cut-off value of 22ng/ml, the sensitivity and specificity of serum LC-SPIK for HCC were 79% and 94% respectively, compared to only 45% and 69% for AFP. Most encouraging, LC-SPIK's accuracy in detecting very early stage HCC (tumor size <2 cm) was 80.0%, compared to only 33% for AFP. The data clearly supports that the technology is significantly better than AFP. We are also confident that HepatoDetect(r) has significant advantages over other current screening and diagnostic methodologies, including many of those still in development. Imaging technologies (CT, MRI, Ultrasound) are operator dependent and very expensive, biopsies are invasive, and developmental technologies such as MDK (midkine) and Gp73 are less specific and are not yet validated.15-19 We propose to further optimize, validate, and complete the development of our HepatoDetect(r) diagnostic kit for clinical use in our phase II study. Procedure: Aim1: We will standardize and optimize our technology and complete development for "HepatoDetect(r) " to screen for HCC. This ELISA kit would be reliable, easy to operate, and inexpensive. Aim2: Using this kit, we will continue to systematically evaluate the performance of LC-SPIK in HCC using a large, double-blinded sample set, which includes 350 HCC specimens and 400 controls from subjects with normal livers, pancreatitis, hepatitis and cirrhosis. The ultimate goal is to receive FDA pre-market approval for this product and to commercialize it. Market: Nearly 5 million people in US and 450 million people worldwide are affected by HBV or HCV, and 30-40% of them are at a high risk of developing HCC. For these people, routine examinations for cancer are necessary. Thus there is a very large market for HCC detection and testing. Competition: Currently, the only diagnostic marker used for HCC detection is AFP, which is significantly less effective than our solution, and there are no other similar products available.