Therapy of solid tumors using probiotic Symbioflor-2 – restraints and potential
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Dino Kocijancic1, Sebastian Felgner1, Michael Frahm1, Ronja-Melinda Komoll1, Aida Iljazovic1, Vinay Pawar1, Manfred Rohde2, Ulrike Heise3, Kurt Zimmermann4, Florian Gunzer5, Juliane Hammer1, Katja Crull1, Sara Leschner1, Siegfried Weiss1,6
1Department of Molecular Immunology, Helmholtz Centre for Infection Research, Braunschweig, Germany
2Central Facility for Microscopy, Helmholtz Centre for Infection Research, Braunschweig, Germany
3Mouse-Pathology Service Unit, Helmholtz Centre for Infection Research, Braunschweig, Germany
4Symbio Gruppe GmbH & Co KG, Herborn, Germany
5Institute of Medical Microbiology and Hygiene, Dresden University of Technology, Dresden, Germany
6Institute of Immunology, Medical School Hannover, Hannover, Germany
Dino Kocijancic, e-mail: [email protected]
Keywords: probiotic, Escherichia coli, bacteria mediated tumor therapy, cancer immune therapy, murine tumor model
Received: January 17, 2016 Accepted: February 25, 2016 Published: March 10, 2016
To date, virulent bacteria remain the basis of most bacteria mediated cancer therapies. For clinical application attenuation is required. However, this might result in a drastically lowered therapeutic capacity. Herein we argue that the E. coli probiotic Symbioflor-2, with a history of safe application may constitute a viable tumor therapeutic candidate. We demonstrate that Symbioflor-2 displays a highly specific tumor targeting ability as determined in murine CT26 and RenCa tumor models. The excellent specificity was ascribed to reduced levels of adverse colonization. A high safety standard was demonstrated in WT and Rag1-/- mice. Thus, Symbioflor-2 may represent an ideal tumor targeting delivery system for therapeutic molecules. Moreover, Symbioflor-2 was capable of inducing CT26 tumor clearance as result of an adjuvant effect on tumor specific CD8+ T cells analogous to the Salmonella variant SL7207. However, lower therapeutic efficacy against RenCa tumors suggested a generally reduced therapeutic potency for probiotics. Interestingly, concurrent depletion of Gr-1+ or Ly6G+ cells installed therapeutic efficacy equal to SL7207, thus highlighting the role of innate effector cells in restraining the anti-tumor effects of Symbioflor-2. Collectively, our findings argue for a strategy of safe strain application and a more sustainable use of bacteria as a delivery system for therapeutic molecules.
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