Attenuated mutant strain of Salmonella Typhimurium lacking the ZnuABC transporter contrasts tumor growth promoting anti-cancer immune response
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Barbara Chirullo1, Serena Ammendola2, Leonardo Leonardi3, Roberto Falcini4, Paola Petrucci1, Claudia Pistoia1, Silvia Vendetti5, Andrea Battistoni2, Paolo Pasquali1
1Department of Veterinary Public Health and Food Safety, Istituto Superiore di Sanità, Rome 00161, Italy
2Department of Biology, University of Rome Tor Vergata, Rome 00133, Italy
3Università degli Studi di Perugia, Department of Veterinary Medicine, Perugia 06126, Italy
4Veterinary Clinic, Rieti 02043, Italy
5Department of Infectious, Parasitic and Immune-Mediated Diseases, Istituto Superiore di Sanità, Rome 00161, Italy
Barbara Chirullo, e-mail: [email protected]
Paolo Pasquali, e-mail: [email protected]
Keywords: bacterial therapy, cancer therapy, antitumor efficacy, attenuated-Salmonella, immune response
Received: February 09, 2015 Accepted: April 24, 2015 Published: May 07, 2015
Salmonella Typhimurium has been shown to be highly effective as antitumor agent. The aim of this study was to investigate the tumor targeting efficacy and the mechanism of action of a specific attenuated mutant strain of Salmonella Typhimurium (STM) devoid of the whole operon coding for the high-affinity zinc transporter ZnuABC, which is required for bacterial growth in environments poor in zinc and for conferring full virulence to different Gram-negative pathogens.
We showed that STM is able to penetrate and replicate into tumor cells in in vitro and in vivo models. The subcutaneous administration of STM in mammary adenocarcinoma mouse model led to both reduction of tumor growth and increase in life expectancy of STM treated mice. Moreover, investigating the potential mechanism behind the favorable clinical outcomes, we provide evidence that STM stimulates a potent inflammatory response and a specific immune pattern, recruiting a large number of innate and adaptive immune cells capable to contrast the immunosuppressive environment generated by tumors.
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