title: Innate immunity based cancer immunotherapy: B16-F10 murine melanoma model.
abstract: Using killed microorganisms or their parts to stimulate immunity for cancer treatment dates back to the end of 19thcentury. Since then, it undergone considerable development. Our novel approach binds ligands to the tumor cell surface, which stimulates tumor phagocytosis. The therapeutic effect is further amplified by simultaneous application of agonists of Toll-like receptors. We searched for ligands that induce both a strong therapeutic effect and are safe for humans.
  
  
  
  B16-F10 murine melanoma model was used. For the stimulation of phagocytosis, mannan or N-formyl-methionyl-leucyl-phenylalanine, was covalently bound to tumor cells or attached using hydrophobic anchor. The following agonists of Toll-like receptors were studied: monophosphoryl lipid A (MPLA), imiquimod (R-837), resiquimod (R-848), poly(I:C), and heat killed Listeria monocytogenes.
  
  
  
  R-848 proved to be the most suitable Toll-like receptor agonist for our novel immunotherapeutic approach. In combination with covalently bound mannan, R-848 significantly reduced tumor growth. Adding poly(I:C) and L. monocytogenes resulted in complete recovery in 83% of mice and in their protection from the re-transplantation of melanoma cells.
  
  
  
  An efficient cancer treatment results from the combination of Toll-like receptor agonists and phagocytosis stimulating ligands bound to the tumor cells.
authors.affiliation: Department of Medical Biology, Faculty of Science, University of South Bohemia, České Budějovice, Czech Republic.
authors.forename: Veronika
authors.initials: V
authors.lastname: Caisová
authors.affiliation: Department of Medical Biology, Faculty of Science, University of South Bohemia, České Budějovice, Czech Republic.
authors.forename: Andra
authors.initials: A
authors.lastname: Vieru
authors.affiliation: Department of Medical Biology, Faculty of Science, University of South Bohemia, České Budějovice, Czech Republic.
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Kumžáková
authors.affiliation: Department of Medical Biology, Faculty of Science, University of South Bohemia, České Budějovice, Czech Republic.
authors.forename: Simona
authors.initials: S
authors.lastname: Glaserová
authors.affiliation: Department of Medical Biology, Faculty of Science, University of South Bohemia, České Budějovice, Czech Republic.
authors.forename: Hana
authors.initials: H
authors.lastname: Husníková
authors.affiliation: Department of Medical Biology, Faculty of Science, University of South Bohemia, České Budějovice, Czech Republic.
authors.forename: Nikol
authors.initials: N
authors.lastname: Vácová
authors.affiliation: Department of Medical Biology, Faculty of Science, University of South Bohemia, České Budějovice, Czech Republic.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Krejčová
authors.affiliation: Department of Medical Biology, Faculty of Science, University of South Bohemia, České Budějovice, Czech Republic.
authors.forename: Lucie
authors.initials: L
authors.lastname: Paďouková
authors.affiliation: 1st Department of Internal Medicine, Medical Faculty of P. J. Šafárik University in Košice, Košice, Slovakia.
authors.forename: Ivana
authors.initials: I
authors.lastname: Jochmanová
authors.affiliation: University of Michigan Medical Center, Ann Arbor, MI, USA.
authors.forename: Katherine I
authors.initials: KI
authors.lastname: Wolf
authors.affiliation: Department of Medical Biology, Faculty of Science, University of South Bohemia, České Budějovice, Czech Republic.
authors.forename: Jindřich
authors.initials: J
authors.lastname: Chmelař
authors.affiliation: Department of Medical Biology, Faculty of Science, University of South Bohemia, České Budějovice, Czech Republic.|Institute of Parasitology, Biology Centre of the Czech Academy of Sciences, v.v.i., České Budějovice, Czech Republic.
authors.forename: Jan
authors.initials: J
authors.lastname: Kopecký
authors.affiliation: Department of Medical Biology, Faculty of Science, University of South Bohemia, České Budějovice, Czech Republic. jzenka@gmail.com.
authors.forename: Jan
authors.initials: J
authors.lastname: Ženka
mesh_terms: D000818:Animals; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D007093:Imidazoles / Q000494:pharmacology; D007113:Immunity, Innate; D007167:Immunotherapy / Q000379:methods; D008024:Ligands; D008351:Mannans / Q000276:immunology; D008546:Melanoma, Experimental; D051379:Mice; D009369:Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D020556:Neutrophil Infiltration / Q000276:immunology; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism; D010587:Phagocytosis; D011070:Poly I-C / Q000276:immunology; D016897:Respiratory Burst / Q000276:immunology; D051193:Toll-Like Receptors / Q000819:agonists / Q000378:metabolism
chemical_list: D016207:Cytokines; D007093:Imidazoles; D008024:Ligands; D008351:Mannans; D051193:Toll-Like Receptors; D011070:Poly I-C; C402365:resiquimod
keywords: Cancer immunotherapy; Innate immunity; Mannan; Melanoma; Neutrophils; Phagocytosis; Resiquimod