Genetically Modified Salmonella Lack Ability to Induce TNF-Alpha and Cause Sepsis According to Nature Biotechnology Publication
NEW HAVEN, CT (December 29, 1998): New research demonstrates that genetic modification of a cell wall component of tumor-targeting Salmonella bacteria can greatly reduce the bacteria's potential for virulence and ability to cause septic shock, announced Vion Pharmaceuticals, Inc. (Nasdaq: VION). Vion is developing the modified bacteria, the heart of the company's TAPET technology, as vectors for the targeted, systemic delivery of anti-cancer agents to tumors throughout the body.
A publication detailing the research, entitled "Lipid A mutant Salmonella with suppressed virulence and TNF-alpha induction retain tumor-targeting in vivo," will appear in the January issue of the journal Nature Biotechnology. The article is authored by scientists at Vion and their collaborators at Yale University School of Medicine; Texas A&M University, College of Veterinary Medicine; and the University of Washington Health Sciences Center.
Vion researchers and their collaborators have previously reported the development of Salmonella that specifically target tumors over normal tissues. However the clinical utility of such bacteria was potentially limited by the ability of lipid A in the bacteria's cell walls to elicit the production of TNF-alpha and trigger septic shock. Now the researchers have shown that a disruption of the Salmonella msbB gene involved in the production of lipid A reduces, by 10,000 fold, the ability of the bacteria's lipid to induce TNF-alpha and cause death in animal models. At the same time, the msbB-minus Salmonella retain their tumor-targeting properties, exhibiting the ability to accumulate in tumors at ratios in excess of 1000:1 compared with normal tissues.
"Administration of these modified bacteria to mice bearing melanoma tumors
results in tumors that are less than six percent the size of tumors in unt
Contact: Joan Kureczka