10075490Intracellular bacterial delivery of therapeutic proteins for treatment of cancerClosedCollaborative 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 and unpleasant side effects. Therefore, it is a top 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 late 2023\. 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 project, Prokarium aims to combine some of the DNA technology and bacterial strains that have already been developed with the natural tendency of Salmonella to enter human cells to engineer a new Trojan horse drug delivery platform that is able to attack cancer cells from within. This approach is designed to either supply new drugs that are released from within the cancer cells (eliminating them in the process) or establish a long-lived depot of drugs that can be released in cycles to maintain long-term therapeutic activity. Ultimately, this work is designed to provide cancer patients with readily available and much needed new therapy options.