Using superselective glycan-binding nanoparticles to create a clinical assay for early ovarian cancer detection

Background Every year, ovarian cancer (OC) kills more than 4 000 women in the UK and 200 000 worldwide. In large part this is due to the fact that most women are not diagnosed until advanced stages. There is an urgent unmet clinical need for diagnostic tools for the early, accurate identification of OC.

OC is associated with alterations in glycosylation of secreted glycoproteins, and as such, they can serve as early OC biomarkers.

There is significant evidence that particular glycans of four different glycoproteins–CA125, immunoglobulin, haptoglobin and transferrin–are closely associated with OC.

However, this knowledge has still not been translated into clinic due to the lack of assays that can differentiate subtle differences between glycan chains.

For the first time, we developed a synthetic glycan recognition platform that can sharply discriminate between different overall glycan structures (Patent No:WO2015/118294).

As a follow on, we have generated superselective glycan-binding nanoparticles and incorporated them in a high-throughput clinical assay. As a proof-of-concept, the studies were conducted to capture the OC associated glycoprotein CA125 from serum.

The assay has undergone a series of optimization steps and analytical validation to ensure reproducible results and sensitivity at clinical levels.

Aim The aim of the project is to use the developed assay to investigate and define, through clinical studies, which of four glycoproteins–CA125, immunoglobulin, haptoglobin and transferrin and respective OC glycans or combination have the highest discriminatory ability for early OC detection.

Methods The experimental work will involve expanding the generation of superselective nanoparticles for the different glycans associated with OC and optimization and validation of the assay for the other three glycoproteins, immunoglobulin, haptoglobin and transferrin. Serum samples from OC patients and controls from women with benign tumours will be tested.

How the results of this research will be used Two phases of clinical evaluation will be needed to develop and validate the novel OC assay.

In Phase 1 (proposed project), we will determine which combination of glycans should be used in the final diagnostic test to best separate patients with OC or not.

In Phase 2, we will pursue further clinical validation by only evaluating the one combination of glycans found to be the most diagnostically useful in Phase 1 evaluation.

This project offers the potential to radically change the diagnostic standard of care for OC, ultimately saving lives and reducing the health, social and economic burden imposed by OC.