The tumour suppressor gene TP53 is mutated in over 50% of human cancers, leading to uncontrolled proliferation of cells. The accumulation of abnormal p53 protein results in the body activating an immune response to produce antibodies that recognise p53 in the blood. These antibodies are attractive biomarkers for early cancer detection since, contrary to the many versions of mutated p53 protein in different cancers, the p53 antibody structure is relatively consistent and so one detection assay can pick up a wide range of cancers. Additionally, p53 antibody levels increase to a much greater extent than the mutated p53 protein and so they are easier to detect over the background level.
In this paper published in ACS Sensors, Professor Jason Davis and his group (Department of Chemistry) have developed an electrochemical sensor that uses nanoparticles coated in peptide sequences from a region of the p53 protein that is rarely mutated. These p53 peptide-coated nanoparticles selectively bind to p53 antibodies from blood serum, which are then isolated and presented to the sensor for quantification.
The researchers demonstrated that this sensor is exceptionally sensitive (femtomolar) and selective in serum samples spiked with purified p53 antibodies. This indicates potential for future clinical translation to detect naturally occurring p53 antibodies in people with cancer.