July 30, 2008 Attenuated Salmonella bacteria engineered to express the Fas ligand (FasL) accumulate in tumors and reduce their growth, researchers report in the July 29 online issue of the Journal of the National Cancer Institute.
Salmonella typhimurium concentrates in tumors following intravenous injection in mice. Taking advantage of that observation, Markus Loeffler, M.D., and John Reed, M.D., Ph.D., of the Burnham Institute for Medical Research in La Jolla, Calif., engineered a genetically modified, less pathogenic strain of Salmonella to express FasL, a signaling protein that can attract neutrophils and can promote tumor cell killing by cytotoxic T cells. Although FasL is toxic when injected into the bloodstream, the authors hypothesized that Salmonella might be used to safely target this protein to tumors.
In the current study, Loeffler, Reed, and colleagues injected mice with tumors derived from mouse breast and colon cancers with attenuated FasL-expressing Salmonella.
Following the treatment, primary tumor growth was substantially inhibited in mice with either breast or colon tumors and lung metastases were reduced in the mice with breast cancer. The anti-cancer effect appeared dependent on the presence of inflammatory cells called neutrophils.
Although toxicology and other studies are needed before the approach can be tested in human clinical trials, "these results from murine cancer models suggest that FasL-expressing [Salmonella] could offer an acceptable strategy for employing FasL and possibly other toxic cytokines for cancer therapy," the authors conclude.
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