Monitoring the progression of cancer in patients is important, but current biomarker diagnostic kits are either expensive or not sensitive enough. A team of Maltese researchers came up with an idea to produce sensitive yet low-cost kits to solve this problem.

This led to the start of a three-year project called FABXS – Development of a Diagnostic Kit for the Quantification of Serum Biomarkers using Fluorescent Affimer Binders. It is being supported under the research and innovation Fusion Technology Development Programme, funded by the government agency Xjenza Malta.

The research team is developing a novel diagnostic kit to quantify a set of oncogenic serum biomarkers, which are proteins present in blood serum of cancer patients.

These biomarkers may be used singly or in combination as prognostic biomarkers of aggressively metastatic cancers, indicators of remission or relapse, and as predictive biomarkers for chemoresistance. Small single-domain antigen-binding proteins known as nanobodies were used in conjunction with specialised chemicals to make them fluorescent to act as sensors, detecting biomarkers in small amounts of body fluids.

Why nanobodies?

Nanobodies function in a way similar to antibodies; however, they have the advantage of being smaller and more stable. Their prolonged shelf-life makes them an attractive system for pharmacological diagnostics. Also, their stability over a range of pH (levels of acidity and basicity) permits their use in different biological samples. The small size of the binders allows them to be inserted into cervices in the three-dimensional structure of the antigen (biomarker in this case), resulting in novel interactions that cannot be accomplished by traditional antibodies.

These nanobodies are produced from a recombinant clone, a small circular DNA that can be introduced in bacteria to start nanobody production. This ensures reproducibility between batches as the synthesised binders will always be identical if the bacteria are grown at the same conditions and the nanobodies are purified in the same conditions.

The expected outcome is the production of the specific, sensitive and affordable components of a diagnostic kit for biomarkers to monitor clinical progression of disease

One of the project’s aims is to keep costs low while maximising sensitivity and reproducibility without the involvement of animals for the production of antibodies. The possibility of monitoring biomarkers at low cost improves societal quality of life.

Moreover, due to the cost-effectiveness and stability of the components the expected outcome is the production of the specific, sensitive and affordable components of a diagnostic kit for biomarkers to monitor clinical progression of disease.

These approaches will result in the development of a prototype kit that can be used to develop commercial products for monitoring cancer progression. Therefore, FABXS hopes to contribute to improving patients’ quality of life and add value to the health sector, which are EU-wide challenges.

The project is a collaborative effort between researchers from the University of Malta, which is the lead partner, and the Sir Anthony Mamo Oncology Centre (SAMOC) at Mater Dei Hospital.

The university team includes Prof. Therese Hunter as principal investigator, Prof. Gary J Hunter and Dr Brandon Charles Seychell from the Department of Physiology and Biochemistry. The SAMOC team led by Dr Nick Refalo.

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