title: Therapy of solid tumors using probiotic Symbioflor-2: restraints and potential.
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.
authors.affiliation: Department of Molecular Immunology, Helmholtz Centre for Infection Research, Braunschweig, Germany.
authors.forename: Dino
authors.initials: D
authors.lastname: Kocijancic
authors.affiliation: Department of Molecular Immunology, Helmholtz Centre for Infection Research, Braunschweig, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Felgner
authors.affiliation: Department of Molecular Immunology, Helmholtz Centre for Infection Research, Braunschweig, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Frahm
authors.affiliation: Department of Molecular Immunology, Helmholtz Centre for Infection Research, Braunschweig, Germany.
authors.forename: Ronja-Melinda
authors.initials: RM
authors.lastname: Komoll
authors.affiliation: Department of Molecular Immunology, Helmholtz Centre for Infection Research, Braunschweig, Germany.
authors.forename: Aida
authors.initials: A
authors.lastname: Iljazovic
authors.affiliation: Department of Molecular Immunology, Helmholtz Centre for Infection Research, Braunschweig, Germany.
authors.forename: Vinay
authors.initials: V
authors.lastname: Pawar
authors.affiliation: Central Facility for Microscopy, Helmholtz Centre for Infection Research, Braunschweig, Germany.
authors.forename: Manfred
authors.initials: M
authors.lastname: Rohde
authors.affiliation: Mouse-Pathology Service Unit, Helmholtz Centre for Infection Research, Braunschweig, Germany.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Heise
authors.affiliation: Symbio Gruppe GmbH & Co KG, Herborn, Germany.
authors.forename: Kurt
authors.initials: K
authors.lastname: Zimmermann
authors.affiliation: Institute of Medical Microbiology and Hygiene, Dresden University of Technology, Dresden, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Gunzer
authors.affiliation: Department of Molecular Immunology, Helmholtz Centre for Infection Research, Braunschweig, Germany.
authors.forename: Juliane
authors.initials: J
authors.lastname: Hammer
authors.affiliation: Department of Molecular Immunology, Helmholtz Centre for Infection Research, Braunschweig, Germany.
authors.forename: Katja
authors.initials: K
authors.lastname: Crull
authors.affiliation: Department of Molecular Immunology, Helmholtz Centre for Infection Research, Braunschweig, Germany.
authors.forename: Sara
authors.initials: S
authors.lastname: Leschner
authors.affiliation: Department of Molecular Immunology, Helmholtz Centre for Infection Research, Braunschweig, Germany.|Institute of Immunology, Medical School Hannover, Hannover, Germany.
authors.forename: Siegfried
authors.initials: S
authors.lastname: Weiss
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D004337:Drug Carriers / Q000494:pharmacology*; D016503:Drug Delivery Systems / Q000379:methods; D004926:Escherichia coli; D051379:Mice; D008807:Mice, Inbred BALB C; D009369:Neoplasms; D019936:Probiotics / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers
keywords: Escherichia coli; bacteria mediated tumor therapy; cancer immune therapy; murine tumor model; probiotic