SubB2M Pan-Cancer Probe

SubB2M

In April 2020 the company, announced it had obtained an exclusive worldwide license to a unique cancer probe called SubB2M. SubB2M is an engineered protein binds to a unique sugar molecule called Neu5Gc which is only present in human cancers. It has the potential to detect cancer using liquid biopsies, immunoassays, circulating tumor cell assays and PET imaging. In initial clinical studies SubB2M has detected cancers with 100% sensitivity and specificity for mid to late-stage cancers, and >95% specificity and 100% sensitivity for early-stage cancers. There is also evidence that the cancer-specific sugar is present in a wide range of solid human tumors and can be detected in serum using SubB2M.

 

Neu5Gc and cancer

The sialic acids are a family of about 30 deriva­tives of neuraminic acid, generated by addition of different substituents at the amino group or at the hydroxyl groups. N-acetylneuraminic acid (Neu 5Ac), the most common neuraminyl derivative, and its hydroxylated derivative N-glycolylneuraminic acid (Neu 5Gc) occur exclusively or together with other sialic acids in tissue type-dependent quantities in almost all higher animals19. Glycans terminating with Neu5Gc are found in animal tissues, fungi, yeast, and bacteria, but are not expressed at significant levels on healthy human tissues, as humans cannot synthesise Neu5Gc due to an inactivating mutation in the CMAH gene. However, elevated Neu5Gc has been observed in tumours, including breast, ovarian, prostate, colon, and lung[1] and pancreatic[2] and endometrial cancers. The presence of Neu5Gc is prognostically important, and correlates with invasiveness, metastasis and tumour grade. As a result, Neu5Gc has been proposed as a tumor antigen, and its detection in human serum and other bodily fluids could be utilised as a diagnostic and prognostic marker in a range of human cancers.

 

Development of a specific probe for Neu5Gc

While there are analytical methods available and a commercially available IgY antibody for the detection of Neu5Gc, researchers at the University of Adelaide engineered (and patented) the B subunit of the bacterial toxin SubAB (which binds to Neu5Gc), to reduce the recognition of Neu5Ac and broaden the recognition of Neu5Gc. This improved Neu5Gc-specific lectin was termed SubB2M. It is a 65kDa pentameric protein. Its enhanced sensitivity and specificity for Neu5Gc has been demonstrated in complex biological samples, including serum. SubB2M lectin therefore offers a potential new tool for the testing of serum and other bodily fluids from individuals with, or suspected of having, cancer[3].

[1] Day CJ, Paton AW, Higgins MA, Shewell LK, Jen FE-C, Schulz BL, Herdman BP, Paton JC, Jennings MP (2017). Structure aided design of a Neu5Gc specific lectin. Nature Scientific Reports; 7: 1495 DOI:10.1038/s41598-017-01522-9

[2] Hedlund M, Padler-Karavani V, Varki NM, Varki A (2008). Evidence for a human-specific mechanism for diet and antibody-mediated inflammation in carcinoma progression Proc Natl Acad Sci U S A; 105(48): 18936–18941.

[3] Wang J, Shewell LK, Paton AW, Paton JC, Day CJ, Jennings MP (2018). Specificity and utility of SubB2M, a new N-glycolylneuraminic acid lectin. Biochem Biophys Res Comm 500: 765-771.