Technology of Glycobond

Background

Hepatocellular carcinoma, HCC, is one of the most prevalent human cancers and the third deadliest with more than 700 000 deaths per year. Currently, only 10 % of all HCC cases are diagnosed at an early stage, which directly correlates to a median survival rate of merely 6-20 months following diagnosis.

The risk of developing HCC is increased in patients with underlying liver disease such as hepatitis, fibrosis and cirrhosis. In addition, HCC is increasing in many countries due to obesity related diseases such as diabetes and metabolic syndrome.

The American Association for the Study of Liver Diseases (AASLD) and the European Association for the Study of the Liver (EASL) recommend surveillance of patients with a high risk of developing HCC; such as patients with cirrhosis and hepatitis infection. Surveillance is today mainly performed by ultrasound every 6 months and with the elevated alpha-fetoprotein (AFP) test.

Early diagnosis is critical for successful treatment. Today, only 10 % of HCC patients are diagnosed at an early stage. Hence, there is an unmet need for diagnostic markers enabling early detection.

Glycobond uses recombinant technology to produce carbohydrate-binding peptides with defined specificities for use primarily in diagnosis and monitoring of liver diseases and cancer.

Our first product is an assay for aid in diagnosis of primary liver cancer.

HepaCheC®

HepaCheC® is an ELISA-based assay that detects aberrant and cancer-specific glycosylation on alpha-1-acid glycoprotein (AGP).

The method is based on a patented fucose-binding protein, Mono-F, developed from the lectin Aleuria aurantia (1-3). Mono-F has a high binding specificity for core and multivalent fucosylation. This type of glycosylation has been implicated as a specific biomarker for HCC (4).

AGP (also known as orosomucoid), is an acute phase plasma glycoprotein primarily synthesized in the liver. Mono-F recognizes HCC-specific glycosylation independent of the protein but detection on AGP was chosen due to 1) the high concentration of AGP in serum from normal individuals (0.8-1.2 g/L; a 1000 times higher than AFP),2) lack of reported genetic deficiencies and 3) lack of multimeric complex formation. HepaCheC® utilizes AGP's high abundancy and extensive glycosylation and detects fucosylated AGP bound to Mono-F by use of a specifically designed primary antibody (in-house invention).

The immunoassay is then completed by using a commercially available product; horseradish peroxidase-conjugated goat anti-rabbit IgG.

1. Olausson et al, Glycoconj J, 2008;25(8):753-62.

2. Olausson et al, Glycobiology, 2011;21(1):34-44.

3. Bergström et al, J Chromatogr B Analyt Technol BiomedLife Sci, 2012;15:885-886:66-72.

4. Tanabe et al, J Proteome Res, 2016;15:2935-2944.

Clinical evaluation

HepaCheC® is considered as a complementary diagnostic method to the elevated AFP or other HCC diagnostic tests. A preliminary study (1) showed very promising results with significant discrimination between cirrhosis and HCC.

We are currently planning and performing post-market performance follow-up studies on HepaCheC to further validate its usefulness in diagnosis of HCC.

1. Åström et al, PLoS One 2017;12(3):e0173897

Collaboration

Glycobond is currently performing PMPF (post market performance follow-up) studies on HepaCheC®. Clinicians and researchers interested in collaboration, please send an e-mail to info@glycobond.com.