Therapy of solid tumors using probiotic Symbioflor-2 - restraints and potential

// Dino Kocijancic 1 , Sebastian Felgner 1 , Michael Frahm 1 , Ronja-Melinda Komoll 1 , Aida Iljazovic 1 , Vinay Pawar 1 , Manfred Rohde 2 , Ulrike Heise 3 , Kurt Zimmermann 4 , Florian Gunzer 5 , Juliane Hammer 1 , Katja Crull 1 , Sara Leschner 1 , Siegfried Weiss 1, 6 1 Department of Molecular Immunology, Helmholtz Centre for Infection Research, Braunschweig, Germany 2 Central Facility for Microscopy, Helmholtz Centre for Infection Research, Braunschweig, Germany 3 Mouse-Pathology Service Unit, Helmholtz Centre for Infection Research, Braunschweig, Germany 4 Symbio Gruppe GmbH & Co KG, Herborn, Germany 5 Institute of Medical Microbiology and Hygiene, Dresden University of Technology, Dresden, Germany 6 Institute of Immunology, Medical School Hannover, Hannover, Germany Correspondence to: Dino Kocijancic, e-mail: dino.kocijancic@helmholtz-hzi.de 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 ABSTRACT 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.