Market Need:
Unlike most mammals, humans cannot synthesise the sialic acid N glycolylneuraminic acid (NeuGc).
Nevertheless, NeuGc is understood to be preferentially taken up by human cancerous cells and subsequently secreted into the blood. Hence, NeuGc represents a specific biomarker for detection of a range of human cancers.
Currently available reagents cannot readily distinguish between NeuGc and other sialic acids commonly found in the human body, resulting in poor specificity and sensitivity.
A highly specific NeuGc-binding ligand will enable early blood based diagnosis of a broad range of tumours including, but not limited to breast, prostate, ovarian, colon and lung.
The Technology:
We have discovered that mutated forms of the (non-toxic) binding subunit of a novel bacterial toxin (SubB) demonstrate unprecedented binding specificity and affinity for NeuGc, without binding to “normal” human sialic acid forms (such as NeuAc).
The research team has developed a large amount of surface plasmon resonance data for 2 mutant variants of the SubB protein, demonstrating either improved specificity and/or sensitivity in binding to the tumour antigen NeuGc over NeuAc.
Data have also been developed using an ELISA based assay using SubB to detect the presence of NeuGc in human serum. We have demonstrated clear dose dependent detection of NeuGc in serum, with sensitivity down to a concentration of 2 nM.
The technology may be used to develop a reagent for use in pathology testing to identify cancerous cells, or ultimately as a broad serum based diagnostic tool for the early identification of cancers.
IP Position:
The underlying bacterial toxin protein, and its mutations are protected by 2 separate patent families:
Australian Patent No. 2004201978 “Cytotoxin with a subtilase domain”; US Patent No. 7,078,489; Canadian Patent No. 2,465,009. This patent family is currently owned by Pentamer Glycoscience Pty Ltd, a start-up company founded by the lead inventors; and
PCT/AU2017/051230 titled “Subtilase Cytotoxin B Subunit Mutant” which covers various mutations of the protein, for which a PCT has been filed. This patent is jointly owned by University of Adelaide and Griffith University.
Commercialisation of the technology will require exploitation of both patent families. As such, processes are underway to consolidate the ownership of the IP into one entity, to streamline commercial engagement.
Next Steps:
Ongoing validation studies are underway in human tissue samples for stage 4 breast, ovarian and prostate cancer, to support development as a diagnostic tool for later stage cancers.
The latest data shows elevated levels of Neu5Gc marker when detected by SubB in our surface plasmon resonance assay in all stage 4 breast cancer and stage 3/4 ovarian cancer, indicating efficacy for use as a serum marker for late-stage progression, as well as for treatment monitoring in late stage patients. The results are significantly stronger than those visible when using a commercially available alternate IgY antibody.
Future studies will review efficacy in early stage samples also, to support development as a broad spectrum diagnostic tool.
The technology offers opportunity for future expansion into products for prognosis and therapeutic treatment of various cancers also. We are actively seeking commercial partners to work with us to develop a diagnostic tool for commercial use.