title: Peritumoral CpG DNA elicits a coordinated response of CD8 T cells and innate effectors to cure established tumors in a murine colon carcinoma model.
abstract: The immune system of vertebrates is able to detect bacterial DNA based on the presence of unmethylated CpG motifs. We examined the therapeutic potential of oligodeoxynucleotides with CpG motifs (CpG ODN) in a colon carcinoma model in BALB/c mice. Tumors were induced by s.c. injection of syngeneic C26 cells or Renca kidney cancer cells as a control. Injection of CpG ODN alone or in combination with irradiated tumor cells did not protect mice against subsequent tumor challenge. In contrast, weekly injections of CpG ODN into the margin of already established tumors resulted in regression of tumors and complete cure of mice. The injection site was critical, since injection of CpG ODN at distant sites was not effective. Mice with two bilateral C26 tumors rejected both tumors upon peritumoral injection of one tumor, indicating the development of a systemic immune response. The tumor specificity of the immune response was demonstrated in mice bearing a C26 tumor and a Renca tumor at the same time. Mice that rejected a tumor upon peritumoral CpG treatment remained tumor free and were protected against rechallenge with the same tumor cells, but not with the other tumor, demonstrating long term memory. Tumor-specific CD8 T cells as well as innate effector cells contributed to the antitumor activity of treatment. In conclusion, peritumoral CpG ODN monotherapy elicits a strong CD8 T cell response and innate effector mechanisms that seem to act in concert to overcome unresponsiveness of the immune system toward a growing tumor.
authors.affiliation: Department of Internal Medicine, Division of Clinical Pharmacology, University of Munich, Munich, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Heckelsmiller
authors.forename: Katharina
authors.initials: K
authors.lastname: Rall
authors.forename: Sebastian
authors.initials: S
authors.lastname: Beck
authors.forename: Angelika
authors.initials: A
authors.lastname: Schlamp
authors.forename: Julia
authors.initials: J
authors.lastname: Seiderer
authors.forename: Bernd
authors.initials: B
authors.lastname: Jahrsdörfer
authors.forename: Anne
authors.initials: A
authors.lastname: Krug
authors.forename: Simon
authors.initials: S
authors.lastname: Rothenfusser
authors.forename: Stefan
authors.initials: S
authors.lastname: Endres
authors.forename: Gunther
authors.initials: G
authors.lastname: Hartmann
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000276:immunology*; D018899:CpG Islands / Q000276:immunology*; D003602:Cytotoxicity, Immunologic / Q000187:drug effects / Q000276:immunology*; D004247:DNA / Q000008:administration & dosage* / Q000276:immunology; D004273:DNA, Neoplasm / Q000008:administration & dosage* / Q000276:immunology; D004195:Disease Models, Animal; D007113:Immunity, Innate / Q000187:drug effects / Q000276:immunology; D007156:Immunologic Memory / Q000187:drug effects / Q000276:immunology; D015552:Injections, Intralesional; D007279:Injections, Subcutaneous; D007680:Kidney Neoplasms / Q000188:drug therapy / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009838:Oligodeoxyribonucleotides
chemical_list: D000970:Antineoplastic Agents; C423449:CpG ODN 1826; D004273:DNA, Neoplasm; D009838:Oligodeoxyribonucleotides; D004247:DNA