Build-a-bug workshop: Using microbial-host interactions and synthetic biology tools to create cancer therapies

• Published in: Cell host & microbe 2023-10, Vol.31 (10), p.1574-1592
• Main Authors: Raman, Vishnu, Deshpande, Chinmay P., Khanduja, Shradha, Howell, Lars M., Van Dessel, Nele, Forbes, Neil S.
• Format: Article
• Language: English
• Subjects: bacterial cancer therapies; Clostridium; E. coli; Listeria; Salmonella; therapeutic design; Yersenia
• ISSN: 1931-3128; 1934-6069
• DOI: 10.1016/j.chom.2023.09.006

Many systemically administered cancer therapies exhibit dose-limiting toxicities that reduce their effectiveness. To increase efficacy, bacterial delivery platforms have been developed that improve safety and prolong treatment. Bacteria are a unique class of therapy that selectively colonizes most solid tumors. As delivery vehicles, bacteria have been genetically modified to express a range of therapies that match multiple cancer indications. In this review, we describe a modular “build-a-bug” method that focuses on five design characteristics: bacterial strain (chassis), therapeutic compound, delivery method, immune-modulating features, and genetic control circuits. We emphasize how fundamental research into gut microbe pathogenesis has created safe bacterial therapies, some of which have entered clinical trials. The genomes of gut microbes are fertile grounds for discovery of components to improve delivery and modulate host immune responses. Future work coupling these delivery vehicles with insights from gut microbes could lead to the next generation of microbial cancer therapy. Several genera of bacteria colonize tumors with high selectivity. New discoveries regarding gut pathogenesis, coupled with advances in synthetic biology, have enabled bacteria to be engineered as safe and effective cancer therapies. Raman et al. describe a “build-a-bug” design method that can be used to create any bacterial cancer therapy.