From vomiting to vaccination: Food poisoning bug used to deliver cancer vaccine

June 22, 2006

By clever design, researchers have devised a way for the bacterium Salmonella typhimurium - often associated with food poisoning - to safely and effectively deliver a vaccine against cancer.

Certain molecules on the surface of cancer cells are either unique or more abundant than those found on non-cancerous cells. These molecules, or antigens, can stimulate the immune system to mount an immune response against the tumor. It is hoped that when a vaccine containing cancer-specific antigens is administered to cancer patients, these antigens will trigger an immune response that targets cancer cells without harming normal cells. Although many cancer vaccine strategies have resulted in measurable immune responses when tested, tumor remission has been observed in only a minority of patients. The identification of new cancer antigens, delivery formulations and vectors is sorely needed.

Since disease-causing bacteria are well equipped to stimulate the immune system, researchers have started to examine the suitability of bacteria that have been genetically manipulated to strip them of their disease-causing ability as delivery vehicles for cancer vaccines. One such bacterium is Salmonella typhimurium, often the culprit in food poisoning in humans. In a study appearing online on June 22 in advance of print publication in the July issue of the Journal of Clinical Investigation, Sacha Gnjatic and colleagues from the Ludwig Institute for Cancer Research constructed an avirulent strain of Salmonella typhimurium endowed with the capacity to deliver the known tumor cell antigen NY-ESO-1. This approach was able to elicit NY-ESO-1-specific CD8+ and CD4+ T cells from lymphocytes taken from cancer patients. Oral delivery of this vaccine to mice resulted in the regression of established NY-ESO-1-expressing tumors. The results of the study suggest that delivery of a cancer vaccine using the Salmonella typhimurium-based delivery system is a promising novel strategy for cancer vaccine development.
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TITLE: In vivo antigen delivery by a Salmonella typhimurium type III secretion system for therapeutic cancer vaccines

AUTHOR CONTACT:
Sacha Gnjatic
Ludwig Institute for Cancer Research, New York, New York, USA.
Phone : (212) 639-8602; Fax: (212) 717-3100; E-mail: gnjatics@mskcc.org.

AUTHOR CONTACT:
Jorge E. Galan
Yale University School of Medicine, New Haven, Connecticut, USA.
Phone : (203) 737-2404; Fax: (203) 737-2630; E-mail: jorge.galan@yale.edu.

View the PDF of this article at: https://www.the-jci.org/article.php?id=28045

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