Improving E. coli-based anti-cancer bacterial therapeutics

Abstract Bacteria-based cancer immunotherapy has existed since Dr. William Coley employed deliberate bacterial infection of tumors over a century ago. Bacteria are inherently immunogenic, self-replicating therapeutics which can be tuned to deliver various payloads, modify specificity, and decrease side effects. Though bacteria are intrinsically capable of selectively colonizing tumor tissue in mouse models, less is understood about the mechanisms behind such colonization. This is especially important as early clinical trials of anti-cancer bacterial therapeutics have been stymied by low colonization rates in human patients. This study aims to identify mechanisms by which E. colievade clearance by the immune system specifically within tumors. Currently, we have screened E. colimutants for tumor colonization efficiency by assessing strain prevalence after recovery from tumors in immunocompetent C57BL/6 mice. We have identified pathways which either promote or inhibit E. colitumor colonization and validated these with competitive infection experiments. This work paves the way for greater understanding of what bacterial mechanisms allow E. colito home to the tumor niche, which may have implications for both developing anti-cancer bacterial therapeutics as well as for understanding how bacteria colonize solid tumors. Supported by grants from NIH (R01 CA249160, T32 GM145440)