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Live bacterial therapeutics is gaining attention, especially for cancer therapy, because anaerobic bacteria selectively grow inside the solid tumours. However, the effect of tumour structure and bacterial characteristics on the pharmacokinetics of tumours is unclear; therefore, we aimed to elucidate the effects of tumour structure and types of bacteria on tumoral bacterial growth. Using six mouse xenograft models, including stroma-rich tumours similar to clinical tumours, and two models of live bacterial therapeutics,  Salmonella typhimurium  VNP20009 and  Escherichia coli  DH5α, we investigated bacterial growth and distribution in tumours after intravenous administration. Rapid growth of  E. coli  was observed in HCT116 and other tumours with few collagens, blood vessels not covered by mural cells, and a cancer cell area proliferated disorderly, whereas tumours with contrasting features, such as BxPC-3, showed lower bacterial growth and a limited intratumor distribution. Alternatively,  Salmonella typhimurium  VNP20009, when successfully proliferated (the probability was approximately 50%), grew to 10 8  colony forming units/g tissue even in BxPC-3 tumours, and its intratumor distribution was extensive. This study suggests that the development of new methods to modify tumour structure will be essential for the development of anti-tumour clinical therapies based on live bacterial therapeutics.

Impact of tumoral structure and bacterial species on growth and biodistribution of live bacterial therapeutics in xenografted tumours