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

Live bacterial therapeutics is gaining attention, especially for cancer therapy, because anaerobic bacteria selectively grow inside the solid tumors. However, the effect of tumor structure and bacterial characteristics on the pharmacokinetics of tumors is unclear; therefore, we aimed to elucidate the effects of tumor structure and types of bacteria on tumoral bacterial growth. Using six mouse xenograft models, including stroma-rich tumors similar to clinical tumors, and two models of live bacterial therapeutics, Salmonella typhimurium VNP20009 and Escherichia coli DH5α, we investigated bacterial growth and distribution in tumors after intravenous administration. Rapid growth of E. coli was observed in HCT116 and other tumors with few collagens, blood vessels not covered by mural cells, and a cancer cell area proliferated disorderly, whereas tumors 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 108 colony forming units/g tissue even in BxPC-3 tumors, and its intratumor distribution was extensive. This study suggests that the development of new methods to modify tumor structure will be essential for the development of anti-tumor clinical therapies based on live bacterial therapeutics.