title: Immunostimulatory CpG oligonucleotides reduce tumor burden after intravesical administration in an orthotopic murine bladder cancer model.
abstract: Bacillus Calmette-Guérin is established in the prophylaxis of recurrent intermediate and high-risk superficial bladder cancer and induces an unspecific, Th1-biased local immune response. Small CpG oligonucleotides (CpG ODN) containing a central unmethylated CpG motif are able to mimic the immunostimulatory activity of bacterial DNA. The purpose of the present study was to evaluate the antineoplastic properties of intravesically administered CpG ODN in an orthotopic murine bladder cancer model. MB49 tumor cell suspension was instilled transurethrally in female C57/BL6 mice on day 0. Mice were divided in three groups of 12 animals. Four mice in each group received either stimulative CpG ODN, non-stimulative GpC ODN or PBS intravesically: group I on day 3, group II on day 5, group III on day 7. After sacrifice 7 days after treatment, bladders were removed and histological examinations were performed. Single instillation of CpG ODN revealed antineoplastic effects in every group demonstrated by significantly lower bladder weight compared with non-stimulative GpC ODN- and PBS-treated mice. Histological examination showed extensive infiltration of macrophages and lymphocytes in CpG ODN-treated mice, whereas PBS- and GpC ODN-treated mice showed solid tumor growth with only few leucocytes. Intravesically applied immunostimulative DNA demonstrated antitumoral activity in an orthotopic murine bladder cancer model. A single instillation seems to be sufficient to reduce tumor load.
authors.affiliation: Department of Urology and Pediatric Urology, Philipps University Marburg, Marburg, Germany. lexaelegeh@aol.com
authors.forename: A
authors.initials: A
authors.lastname: Hegele
authors.forename: A
authors.initials: A
authors.lastname: Dalpke
authors.forename: K
authors.initials: K
authors.lastname: Heeg
authors.forename: P
authors.initials: P
authors.lastname: Barth
authors.forename: Z
authors.initials: Z
authors.lastname: Varga
authors.forename: R
authors.initials: R
authors.lastname: Hofmann
authors.forename: P
authors.initials: P
authors.lastname: Olbert
mesh_terms: D000818:Animals; D001500:BCG Vaccine / Q000276:immunology; D002295:Carcinoma, Transitional Cell / Q000235:genetics* / Q000503:physiopathology* / Q000662:veterinary; D018899:CpG Islands; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D009841:Oligonucleotides / Q000627:therapeutic use*; D018417:Th1 Cells / Q000276:immunology*; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000503:physiopathology* / Q000662:veterinary
chemical_list: D001500:BCG Vaccine; D009841:Oligonucleotides