Bacterial cancer therapy (BCT) is an immunotherapy strategy that uses attenuated bacterial strains to suppress tumor growth. While the strains are attenuated, there is still a safety risk associated with their use, and this has prompted investigation into alternative BCT methods. In a recent Science Translational Medicine publication, researchers have actually engineered a bacterium to fight tumors by overexpressing and unlikely protein. In this paper, flagellin protein (FlaB) was overexpressed in Salmonella typhimurium strains. The rationale behind this was that flagellin is known to activate immune responses via Toll-like receptors, specifically TLR5, which would make it a good cancer immunotherapy candidate. These modified bacteria were delivered into tumors in mice, and the impact on tumor volume and TLR signaling was analyzed. The authors discovered that following delivery of the engineered Salmonella, there was a localized increase in immune cells, such as monocytes and macrophages, as a result of TLR4 signaling. Subsequently, the increased immune response inhibited metastasis and tumor growth, further promoting recovery in mice without any deleterious effects from the microbes. Together, these results provide renewed support behind the use of modified bacteria for cancer therapy.
Zheng et al. Two-step enhanced cancer immunotherapy with engineered Salmonella typhimurium secreting heterologous flagellin. Science Translational Medicine. 2017. DOI: 10.1126/scitranslmed.aak953