Comparative evaluation of anticancer efficacy and tissue distribution of tumor-targeting Salmonella typhimurium delivered systemically or orally in murine models

摘要

Tumor-targeting Salmonella typhimurium VNP20009 has been systemically administrated as a single-agent therapy at doses of over 1 ×106 cfu/mouse, as a part of combination therapy at doses of over 1×104 cfu/mouse, or orally delivered for cancer therapy at a dose of 1 × 109 cfu/mouse. Here we performed a comparative evaluation of anticancer efficacy and tissue toxicity of VNP20009 administrated intraperitoneally with doses of 1 × 106 cfu/mouse (VNP6-i. p. ), 1× 104cfu/mouse (VNP4-i. p. ), or orally with a dose of 1 × 109cfu/mouse (VNP9-oral). VNP6-i. p. resulted in significant toxicities and higher bacteria titer in normal tissues, although it induced the best anticancer effect. VNP4-i. p. and VNP9-oral induced similar anticancer effect, Compared to VNP4-i. p, VNP9-oral induced milder toxicity and lower bacteria titer in tissues. Compared to conventionally systemic infection, oral administration, as an alternative route for bacterial administration, displayed high safety.