10112670Next generation living cures for cancer immunotherapyClosedCollaborative R&DInnovate UKCancer occurs when cells in the body accumulate genetic mutations that prompt them to grow uncontrollably, affecting normal body functions and potentially leading to death. Acquiring such mutations, and therefore developing a cancer, is more probable as we age. It is estimated that 1 in 2 people will experience cancer in their lifetime. Most standard cancer treatments, such as chemotherapy and radiotherapy, are associated with significant unpleasant side effects. Therefore, it is a high priority to help patients overcome cancer without having to rely on toxic drugs that severely affect their quality of life. The use of microbe-based immunotherapy for cancer treatment was first described in the late 19th century, and the current standard of care for bladder cancer, the bacterial therapy using the Bacillus Calmette-Guerin (BCG) was medically established in the 1920s. However, a lack of molecular tools and the increasing popularity of radiotherapy in a pre-penicillin world stalled further microbial immunotherapy research. Now, with modern synthetic and molecular biology tools and technologies, the approach of using bacteria to train a patient's own immune system to recognise and fight cancer cells has re-emerged. Using cutting-edge bioengineering technologies, Prokarium has developed a treatment platform based on safe, attenuated _Salmonella_ bacteria capable of navigating towards and colonising the tumour environment, with a promising first product reaching bladder cancer patients in early 2024. Through an ongoing partnership with the London Biofoundry, Prokarium have set up a pipeline that can load Salmonella with modular protein blocks that can be delivered to tumours and expressed by tumour-associated cells to activate or suppress different elements of the immune system. In this proposal, Prokarium aims to advance this technology to control precisely where these therapeutic payloads are delivered and incorporate smart sensors that control and stagger how much is released to ensure long-term activity. These new payloads will be tailored to each type of cancer by testing multiple bacterial strains to ensure the optimal match between each tumour and the most effective strain for sustained effective delivery, creating a precision medicine for each cancer type and providing patients with access to more advanced therapy options.