NEW YORK – A team of researchers at the University of Bristol in the UK has been awarded £500,000 ($640,000) to support the development of a new blood-based test for the early diagnosis of brain cancer. The researchers envisage deploying a point-of-care assay based on a fluorescent nanophotonics platform.
Cancer Research UK is funding the project, which is slated to run through 2024 and will commence next month.
Kathreena Kurian, an associate professor in brain tumor research at the University of Bristol, is leading the project. She said there is a need for a blood-based, point-of-care test in the UK, where it often takes multiple visits to a general practitioner before a patient presenting with symptoms is referred to a hospital for a CT scan or MRI. Of those referred, most are negative.
"For every 4,000 headaches, there's probably one that has a serious neurological condition attached," said Kurian. "There are lots of worried well getting negative scans," she said. "That is also a burden to the [National Health Service] system."
By delivering a blood test to market that can be carried out by British GPs, the researchers hope to transform the way brain tumors are diagnosed, trim NHS costs, and catch cancers earlier. They also believe such a blood-based test could be used to track recurrence.
The initial focus of the new CRUK-backed project will be to transition a marker that Kurian's team has used regularly in the lab to a new platform where it can be used at the point of care. The glial fibrillary acidic protein (GFAP) marker is the team's diagnostic "baseline," which according to Kurian, is a "well-worked up" reliable molecule for diagnosis. However, the current means of measuring GFAP — enzyme-linked immunosorbant assays — are not specific enough for the researchers, and they have to be processed in a centralized laboratory, not at the GP's office.
"ELISAs are time consuming," added Kurian.
The researchers have also developed other antibodies of interest for use in diagnosis, but it's the same story. ELISA is not capable of delivering the sensitivity or speed for a quick diagnosis. To overcome this, they have turned to Fluoretiq, a Bristol-based company, as a technology partner.
Fluoretiq has been developing a rapid test called Nanoplex for diagnosing bacterial infections and guiding antibiotic treatment selection. However, the partners believe the same technology can be repurposed for detecting markers associated with brain cancer in patients' blood samples.
The company's platform relies on the use of fluorescent carbon dots that can be attached to ligands, including antibodies targeting protein biomarkers, such as GFAP. These labeled markers can then be detected using nanophotonics, the study of the behavior of light on the nanometer scale. Based on metrics obtained via the Fluoretiq assay, the researchers hope to be able to not only diagnose patients, but also to predict the size of the tumor.
The researchers aim is that by 2024, when the current project concludes, they will have optimized a nanoparticle diagnostic for clinical use.
"Once we have developed GFAP on a nanoparticle, in an ideal world the blood sample will be drawn, spun, and the plasma will be added to the Fluoretiq platform," said Kurian. "Their technology is great and we are creating different nanoparticles," she said. "It would also be quicker than an ELISA and it would be sensitive to pick up tiny amounts of protein."
The team's ambitions do not end there. They are also planning to develop nucleic acid-based diagnostics for brain cancer,although these plans are at an early stage, Kurian said. Plans are underway to undertake genome-wide association studies of brain cancer samples in order to seek out single nucleotide variant (SNV) signatures that could be used to diagnose or guide treatment. Kurian declined to elaborate further, and stressed the work is preliminary.
By the end of the grant, the University of Bristol team does hope to have developed other diagnostics beyond the GFAP assay on the Fluoriteq platform, Kurian said. To validate any other tests, it would need additional funding for a cohort study and might look for support from British R&D funding agencies such as Innovate UK.
Fluoretiq new to cancer
Fluoretiq's technology was developed at the University of Bristol in the laboratory of Carmen Galan, a professor of organic and biological chemistry at the university, who is also taking part in the new CRUK-funded project. The company was spun out of the university three years ago, and Neciah Dorh has served as its CEO since that time. Dorh currently leads a team of six, and the company's main focus is preparing a test for urinary tract infection on the Nanoplex platform, with a follow-on assay for antibiotic susceptibility testing in its pipeline.
Oncology is a new area for the company, but Dorh said it fits with Fluoretiq's ethos of "using technology to help improve people's lives." The firm has already built an assay around the GFAP marker that can be run using a low-cost fluorometer.
Like Kurian, Dorh stressed that the work around brain cancer is preliminary. "This is at an early, feasibility stage," he said. "We hope to develop it into a commercial product," he added, "but this is a longterm view."
In the meantime, the company will continue with its push to have its UTI test on the market soon. By the time the CRUK project wraps up, Dorh said that Fluoretiq aims to have its test available in the UK and internationally and to be assessing other applications.