10105273Development and validation of a tumour inducible promoter platform for engineered live biotherapeuticsClosedCollaborative R&DInnovate UKNeobe Therapeutics is an early-stage start up developing a synthetic biology platform to enable immunotherapy success in currently non responding cancer patients. Our platform is based on safe strains of tumour colonizing bacteria, which are engineered to be activated within solid tumours to release payloads that remove local barriers to immune infiltration. By increasing the number of immune cells that are able to penetrate solid tumours and reach cancer cells, Neobe's products can exponentially increase the number of patients that respond to existing immunotherapeutic approaches, without affecting healthy tissues. In order to achieve this localized tumour remodelling, a central part of this platform is the engineering of effective and specific molecular biosensors, enabling product activation in the tumour microenvironment alone. Initial work by the Neobe team has generated an initial promoter library, and demonstrated that optimizing specific regions of the promoter sequence can increase the specificity of promoter activation. This project builds on that data, using started of the art high throughput facilities at the London Biofoundry to engineer and screen an extended library of tumour inducible promoters. Synthetic biology will be used to generate more advanced engineered promoter elements, which will increase the efficacy, containment and safety of Neobe's products as an essential part of its clinical development package. Engineered promoter elements will be tested for their specific tumour inducible responses in vitro and in vivo. The project will be led by Neobe's team, which is uniquely suited to guarantee its success due to its joint expertise in bacterial engineering, cancer biology and therapeutic commercialization. Work will also be performed at the London Biofoundry's state of the art facilities for engineering biology, providing the necessary capabilities for high-throughput candidate generation and screening. Lead candidates will be tested in vivo and selected for their capability for enhanced and specific activation, to be later combined with Neobe's lead therapeutic candidates. This project's success will be an important stepping stone in the development of Neobe's first in class engineered therapeutic product for cancer patients. This could have significant impacts in the lives of cancer patients, by expanding the tremendous therapeutic benefits of immunotherapies to non-responders, as well as contribute to the rise of the UK as a leader in the use of synthetic biology to generate safer and more effective therapeutic products.