PT  - JOURNAL ARTICLE
AU  - YASUNORI TOME
AU  - YONG ZHANG
AU  - MASASHI MOMIYAMA
AU  - HIROKI MAEHARA
AU  - FUMINORI KANAYA
AU  - KATSURO TOMITA
AU  - HIROYUKI TSUCHIYA
AU  - MICHAEL BOUVET
AU  - ROBERT M. HOFFMAN
AU  - MING ZHAO
TI  - Primer Dosing of <em>S. typhimurium</em> A1-R Potentiates Tumor-Targeting and Efficacy in Immunocompetent Mice
DP  - 2013 Jan 01
TA  - Anticancer Research
PG  - 97--102
VI  - 33
IP  - 1
4099  - http://ar.iiarjournals.org/content/33/1/97.short
4100  - http://ar.iiarjournals.org/content/33/1/97.full
SO  - Anticancer Res2013 Jan 01; 33
AB  - We developed the tumor-targeting strain Salmonella typhimuium A1-R (A1-R) and have shown it to be active against a number of tumor types in nude mice. However, in immunocompetent mice, dosing of A1-R has to be adjusted to avoid toxicity. In the present study, we developed a strategy to maximize efficacy and minimize toxicity for A1-R tumor-targeting in immunocompetent mice implanted with the Lewis lung carcinoma. A small primer dose of A1-R was first administered (1×106 colony forming unit [cfu] i.v.) followed by a high dose (1×107 cfu i.v.) four hours later. The primer-dose strategy resulted in smaller tumors and no observable side-effects compared to treatment with high-dose-alone. The serum level of tumor necrosis factor (TNF-α) was elevated in the mice treated with primer dose compared to mice only given the high dose. Tumor vessel destruction was enhanced by primer dosing of A1-R in immuno-competent transgenic mice expressing the nestin-driven green fluorescent protein, which is selectively expressed in nascent blood vessels. The primer-dose may activate TNF-α and other cytokines in the mouse, necessary for invasion of the tumor by the bacteria, as well as enhance tumor vessel destruction, thereby allowing a subsequent therapeutic dose to be effective and safe. The results of the present study suggest effective future clinical strategies of bacterial treatment of cancer.