Convincing preclinical studies and our clinical trial data demonstrate that certain bacteria, including the probiotic E. coli Nissle 1917 selectively colonise tumours, rather than normal tissue. Understanding these niche specific behaviours of microbes, together with advances in bacterial engineering, have catalysed the development of living cell diagnostics and therapeutics. This has included microbes that respond to diseases such as gut inflammation, intestinal bleeding, pathogens and hypoxic tumors.
Our team and others have engineered tumour homing bacteria to selectively release combinations of pro-apoptotic, cytotoxic and immune-activating payloads in tumours, with validated reductions in off-target toxicity through tumour directed delivery and anti-tumour and survival benefits in mouse models of cancer. Here we develop engineered probiotics to produce screening and therapeutic molecules, resulting in non-invasive detection of precursor lesions for bowel cancer. We are expanding on these studies using alternate bacterial chassis species, to develop living biosensors engineered to detect specific cancer associated DNA sequences. Our findings establish a framework for biosensing applications that require the detection of mutations or organisms within environments that are difficult to sample, or for screening. Importantly, the platform is modular in nature, so can be readily expanded to include in situ production and delivery of therapeutic payloads at the detection site.