Arthur M Krieg

Summary

Affiliation: Coley Pharmaceutical Group

Publications

  1. ncbi request reprint Antitumor applications of stimulating toll-like receptor 9 with CpG oligodeoxynucleotides
    Arthur M Krieg
    Coley Pharmaceutical Group, 93 Worcester Street, Suite 101, Wellesley, MA 02481, USA
    Curr Oncol Rep 6:88-95. 2004
  2. doi request reprint Toll-like receptor 9 (TLR9) agonists in the treatment of cancer
    A M Krieg
    Coley Pharmaceutical Group Inc, Wellesley, MA 02481, USA
    Oncogene 27:161-7. 2008
  3. pmc Immunostimulatory effects of three classes of CpG oligodeoxynucleotides on PBMC from HCV chronic carriers
    Curtis L Cooper
    Coley Pharmaceutical Canada, Ottawa, Canada
    J Immune Based Ther Vaccines 6:3. 2008
  4. ncbi request reprint From A to Z on CpG
    Arthur M Krieg
    Coley Pharmaceutical Group, Wellesley, MA 02481, USA
    Trends Immunol 23:64-5. 2002
  5. ncbi request reprint P-chirality-dependent immune activation by phosphorothioate CpG oligodeoxynucleotides
    Arthur M Krieg
    Department of Internal Medicine, University of Iowa, and Veterans Affairs Medical Center, Iowa City, USA
    Oligonucleotides 13:491-9. 2003
  6. ncbi request reprint From bugs to drugs: therapeutic immunomodulation with oligodeoxynucleotides containing CpG sequences from bacterial DNA
    A M Krieg
    Department of Veterans Affairs Medical Center, Iowa City, IA 52246, USA
    Antisense Nucleic Acid Drug Dev 11:181-8. 2001
  7. ncbi request reprint CpG DNA: trigger of sepsis, mediator of protection, or both?
    Arthur M Krieg
    Coley Pharmaceutical Group, Wellesley, Massachusetts 02481, USA
    Scand J Infect Dis 35:653-9. 2003
  8. ncbi request reprint Induction of systemic TH1-like innate immunity in normal volunteers following subcutaneous but not intravenous administration of CPG 7909, a synthetic B-class CpG oligodeoxynucleotide TLR9 agonist
    Arthur M Krieg
    Coley Pharmaceutical Group, Wellesley, Massachusetts 02481, USA
    J Immunother 27:460-71. 2004
  9. pmc Development of TLR9 agonists for cancer therapy
    Arthur M Krieg
    Coley Pharmaceutical Group, 93 Worcester Street, Wellesley, MA 02481, USA
    J Clin Invest 117:1184-94. 2007
  10. ncbi request reprint CpG motifs: the active ingredient in bacterial extracts?
    Arthur M Krieg
    Coley Pharmaceutical Group, Wellesley, Massachusetts 02481, USA
    Nat Med 9:831-5. 2003

Detail Information

Publications90

  1. ncbi request reprint Antitumor applications of stimulating toll-like receptor 9 with CpG oligodeoxynucleotides
    Arthur M Krieg
    Coley Pharmaceutical Group, 93 Worcester Street, Suite 101, Wellesley, MA 02481, USA
    Curr Oncol Rep 6:88-95. 2004
    ..This review describes the immune effects of synthetic CpG oligonucleotides as TLR9 ligands and their applications in cancer immunotherapy...
  2. doi request reprint Toll-like receptor 9 (TLR9) agonists in the treatment of cancer
    A M Krieg
    Coley Pharmaceutical Group Inc, Wellesley, MA 02481, USA
    Oncogene 27:161-7. 2008
    ..The activity and safety of these novel anticancer agents are being explored in a wide range of tumor types as part of a variety of therapeutic strategies with the goal of harnessing the immune response to fight cancer...
  3. pmc Immunostimulatory effects of three classes of CpG oligodeoxynucleotides on PBMC from HCV chronic carriers
    Curtis L Cooper
    Coley Pharmaceutical Canada, Ottawa, Canada
    J Immune Based Ther Vaccines 6:3. 2008
    ..A potent immune activator such as TLR9 agonist CpG oligodeoxynucleotide (CpG) may complement current treatment approaches...
  4. ncbi request reprint From A to Z on CpG
    Arthur M Krieg
    Coley Pharmaceutical Group, Wellesley, MA 02481, USA
    Trends Immunol 23:64-5. 2002
  5. ncbi request reprint P-chirality-dependent immune activation by phosphorothioate CpG oligodeoxynucleotides
    Arthur M Krieg
    Department of Internal Medicine, University of Iowa, and Veterans Affairs Medical Center, Iowa City, USA
    Oligonucleotides 13:491-9. 2003
    ..Rp-chirality at the CpG is preferred for best stimulation at early time points, but Sp-chirality of the PS-oligo appears to improve stability and may provide more durable effects in prolonged tissue culture systems...
  6. ncbi request reprint From bugs to drugs: therapeutic immunomodulation with oligodeoxynucleotides containing CpG sequences from bacterial DNA
    A M Krieg
    Department of Veterans Affairs Medical Center, Iowa City, IA 52246, USA
    Antisense Nucleic Acid Drug Dev 11:181-8. 2001
    ..Human clinical trials using such CpG DNA are currently underway...
  7. ncbi request reprint CpG DNA: trigger of sepsis, mediator of protection, or both?
    Arthur M Krieg
    Coley Pharmaceutical Group, Wellesley, Massachusetts 02481, USA
    Scand J Infect Dis 35:653-9. 2003
    ..Under other conditions, the immune stimulatory effects of CpG motifs can protect against pathogen challenge and initiate prophylactic and therapeutic innate and adaptive immune responses...
  8. ncbi request reprint Induction of systemic TH1-like innate immunity in normal volunteers following subcutaneous but not intravenous administration of CPG 7909, a synthetic B-class CpG oligodeoxynucleotide TLR9 agonist
    Arthur M Krieg
    Coley Pharmaceutical Group, Wellesley, Massachusetts 02481, USA
    J Immunother 27:460-71. 2004
    ..These studies indicate that in vivo activation of TLR9 by subcutaneous administration of CPG 7909 could be a well-tolerated immunotherapeutic approach for induction of TH1 innate immune activation...
  9. pmc Development of TLR9 agonists for cancer therapy
    Arthur M Krieg
    Coley Pharmaceutical Group, 93 Worcester Street, Wellesley, MA 02481, USA
    J Clin Invest 117:1184-94. 2007
    ....
  10. ncbi request reprint CpG motifs: the active ingredient in bacterial extracts?
    Arthur M Krieg
    Coley Pharmaceutical Group, Wellesley, Massachusetts 02481, USA
    Nat Med 9:831-5. 2003
    ..Identification of these receptors and the molecular signaling pathways that they activate has enabled a new era of specific targeted immunotherapy using chemically synthesized mimics of pathogen molecules...
  11. pmc Antiinfective applications of toll-like receptor 9 agonists
    Arthur M Krieg
    Coley Pharmaceutical Group, Inc, 93 Worcester Street, Suite 101, Wellesley, MA 02481, USA
    Proc Am Thorac Soc 4:289-94. 2007
    ....
  12. ncbi request reprint CpG motifs in bacterial DNA and their immune effects
    Arthur M Krieg
    Department of Veterans Affairs Medical Center, Iowa City, Iowa 52246, USA
    Annu Rev Immunol 20:709-60. 2002
    ..CpG ODN also enhance the development of acquired immune responses for prophylactic and therapeutic vaccination...
  13. ncbi request reprint Toll-like receptors 7, 8, and 9: linking innate immunity to autoimmunity
    Arthur M Krieg
    Coley Pharmaceutical Group Inc, Wellesley, MA, USA
    Immunol Rev 220:251-69. 2007
    ..Finally, with the rapid progress in the development of therapeutic agonists for the TLRs, there is accompanying attention to the theoretical possibility that such therapy may induce autoimmunity or autoimmune diseases...
  14. ncbi request reprint The toll of too much TLR7
    Arthur M Krieg
    Coley Pharmaceutical Group, 93 Worcester Street, Suite 101, Wellesley, MA 02481, USA
    Immunity 27:695-7. 2007
    ..Toll-like receptor 7 (TLR7) detects viral RNA, but can be activated inappropriately by self-RNA, leading to autoimmunity. Deane et al. (2007) show that Tlr7 gene dosage is directly related to the risk of lupus in a mouse model...
  15. doi request reprint Immunology. The toll of cathepsin K deficiency
    Arthur M Krieg
    Coley Pharmaceutical Group, 93 Worcester Street, Wellesley, MA 02481, USA
    Science 319:576-7. 2008
  16. ncbi request reprint Therapeutic potential of Toll-like receptor 9 activation
    Arthur M Krieg
    Coley Pharmaceutical Group, Inc, 93 Worcester Street, Suite 101, Wellesley, Massachusetts 02481, USA
    Nat Rev Drug Discov 5:471-84. 2006
    ....
  17. ncbi request reprint Surgical excision combined with autologous whole tumor cell vaccination is an effective therapy for murine neuroblastoma
    Kensuke Ohashi
    Department of Surgery, Roy J and Lucille A Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA
    J Pediatr Surg 41:1361-8. 2006
    ....
  18. ncbi request reprint Inhibitory oligonucleotides block the induction of AP-1 transcription factor by stimulatory CpG oligonucleotides in B cells
    Petar Lenert
    Department of Internal Medicine, University of Iowa, College of Medicine, Iowa City, IA 52242, USA
    Antisense Nucleic Acid Drug Dev 13:143-50. 2003
    ..These data suggest that inhibitory ODNs block the CpG ODN-driven signaling pathway at a site proximal to AP-1 induction...
  19. ncbi request reprint TLR9 is required for protective innate immunity in Gram-negative bacterial pneumonia: role of dendritic cells
    Urvashi Bhan
    Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine, University of Michigan Medical Center, Ann Arbor, MI 48109, USA
    J Immunol 179:3937-46. 2007
    ....
  20. ncbi request reprint Safety, pharmacokinetics and immune effects in normal volunteers of CPG 10101 (ACTILON), an investigational synthetic toll-like receptor 9 agonist
    Alain P Vicari
    Coley Pharmaceutical Group, Wellesely, MA, USA
    Antivir Ther 12:741-51. 2007
    ..CPG 10101 (ACTILON) is a novel potent and selective unmethylated cytidine-phosphate-guanosine (CpG)-containing oligodeoxynucleotide agonist of Toll-like receptor 9 (TLR9) being developed for the treatment of chronic infections such as HCV...
  21. ncbi request reprint Chronic ethanol ingestion by mice increases expression of CD80 and CD86 by activated macrophages
    Xiaoyan Zhu
    Department of Pathology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA
    Alcohol 32:91-100. 2004
    ..Such cells may contribute to systemic immunodysregulation, including T-cell activation, by providing abnormal second signals to T cells, or through excessive release of cytokines, such as interleukin (IL)-6 or IL-12...
  22. ncbi request reprint CpG-A-induced monocyte IFN-gamma-inducible protein-10 production is regulated by plasmacytoid dendritic cell-derived IFN-alpha
    Sue E Blackwell
    Department of Internal Medicine, University of Iowa, Iowa City, IA 52242, USA
    J Immunol 170:4061-8. 2003
    ..These studies provide a better understanding of the mechanisms through which CpG ODN create a Th1-like environment...
  23. ncbi request reprint Oligodeoxynucleotide CpG 7909 delivered as intravenous infusion demonstrates immunologic modulation in patients with previously treated non-Hodgkin lymphoma
    Brian K Link
    Department of Internal Medicine, Holden Comprehensive Cancer Center, University of Iowa, 200 Hawkins Drive, Iowa City, IA 52242, USA
    J Immunother 29:558-68. 2006
    ..Two subjects demonstrated late response. We conclude CpG 7909 can be safely given as a 2-hour IV infusion to patients with previously treated non-Hodgkin lymphoma at doses that have immunomodulatory effects...
  24. ncbi request reprint Paradoxical enhancement of CD8 T cell-dependent anti-tumor protection despite reduced CD8 T cell responses with addition of a TLR9 agonist to a tumor vaccine
    Dev Karan
    VA Medical Center, Iowa City, IA, USA
    Int J Cancer 121:1520-8. 2007
    ..In addition, the results indicate that widely used standard immune parameters may not predict the vaccine efficacy containing a TLR9 agonist as adjuvant...
  25. doi request reprint CpG still rocks! Update on an accidental drug
    Arthur M Krieg
    RaNA Therapeutics, Inc, Cambridge, Massachusetts 02141, USA
    Nucleic Acid Ther 22:77-89. 2012
    ..Along with many positive results have come some failures showing the limitations of several therapeutic approaches. This review summarizes these results to provide an overview of the clinical development of CpG ODN...
  26. pmc CpG oligodeoxynucleotides stimulate protective innate immunity against pulmonary Klebsiella infection
    Jane C Deng
    Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine, University of Michigan Medical Center, Ann Arbor 48109, USA
    J Immunol 173:5148-55. 2004
    ..t. administration of CpG ODN can stimulate multiple components of innate immunity in the lung, and may form the basis for novel therapies directed at enhancing protective immune responses to severe bacterial infections of the lung...
  27. ncbi request reprint Induction of autoantibody production but not autoimmune disease in HEL transgenic mice vaccinated with HEL in combination with CpG or control oligodeoxynucleotides
    Yiqiang Wang
    Department of Internal Medicine, University of Iowa College of Medicine, 200 Hawkins Drive, Iowa City, IA 52242, USA
    Vaccine 22:2641-50. 2004
    ..We conclude that immunization with CpG or control ODN in the presence of a high dose of exogenous self antigen, but not treatment with ODN alone, can break tolerance to self antigen without inducing autoimmune disease in this system...
  28. ncbi request reprint Synergy between CpG- or non-CpG DNA and specific antigen for B cell activation
    Yiqiang Wang
    Department of Internal Medicine, University of Iowa College of Medicine, 200 Hawkins Drive, Iowa City, IA 52242, USA
    Int Immunol 15:223-31. 2003
    ....
  29. ncbi request reprint Accumulation of glutathione disulfide mediates NF-kappaB activation during immune stimulation with CpG DNA
    Jeffrey D Kirsch
    Department of Internal Medicine, University of Iowa, Iowa City 52242, USA
    Antisense Nucleic Acid Drug Dev 12:327-40. 2002
    ..These data suggest the existence of a second CpG-induced intracellular signal, independent of GSSG, mediating the activation of innate immunity by bacterial DNA...
  30. ncbi request reprint Antibody repertoire development in fetal and neonatal piglets. IX. Three pathogen-associated molecular patterns act synergistically to allow germfree piglets to respond to type 2 thymus-independent and thymus-dependent antigens
    John E Butler
    Department of Microbiology and Interdisciplinary Immunology Program, University of Iowa, Iowa City, IA 52242, USA
    J Immunol 175:6772-85. 2005
    ....
  31. doi request reprint Toll-like receptor 9 activation with CpG oligodeoxynucleotides for asthma therapy
    Joel N Kline
    Department of Medicine, Carver College of Medicine, University of Iowa, Iowa City, Iowa 52242, USA
    Drug News Perspect 21:434-9. 2008
    ....
  32. pmc Oral pretreatment of mice with CpG DNA reduces susceptibility to oral or intraperitoneal challenge with virulent Listeria monocytogenes
    Nancy B Ray
    Department of Internal Medicine, University of Iowa, Iowa City, Iowa 52242, USA
    Infect Immun 71:4398-404. 2003
    ..These results indicate that oral administration of CpG DNA induces systemic innate immune defenses against either oral or systemic infection with virulent L. monocytogenes...
  33. ncbi request reprint B cells express Ly-6C in a Th1 but not Th2 cytokine environment
    Annette J Schlueter
    Department of Pathology, University of Iowa College of Medicine, Iowa City, IA 52242 1181, USA
    J Interferon Cytokine Res 22:799-806. 2002
    ..1 and Ly6.2 strains...
  34. ncbi request reprint Impact of modifications of heterocyclic bases in CpG dinucleotides on their immune-modulatory activity
    Jorg Vollmer
    Coley Pharmaceutical, Elisabeth Selbert Str 9, 40764 Langenfeld, Germany
    J Leukoc Biol 76:585-93. 2004
    ..These studies provide a structure-activity relationship for TLR9 agonist compounds with diverse immune effects...
  35. ncbi request reprint C-Class CpG ODN: sequence requirements and characterization of immunostimulatory activities on mRNA level
    Marion Jurk
    Coley Pharmaceutical GmbH, Elisabeth Selbert Str 9, D 40764 Langenfeld, Germany
    Immunobiology 209:141-54. 2004
    ..These characteristics can be availed to induce potent anti-tumor or anti-viral effects. Consequently, C-Class CpG ODN represent ideal drug candidates for anti-viral and/or anti-tumor therapy...
  36. ncbi request reprint Modulating responsiveness of human TLR7 and 8 to small molecule ligands with T-rich phosphorothiate oligodeoxynucleotides
    Marion Jurk
    Coley Pharmaceutical GmbH, Langenfeld, Germany
    Eur J Immunol 36:1815-26. 2006
    ..These results demonstrate an unexpected plasticity in the ligand specificities of TLR7 and TLR8, and suggest a novel sequence-selective interaction between these receptors and synthetic phosphorothioate ODN...
  37. pmc Immunopharmacology of CpG oligodeoxynucleotides and ribavirin
    Jorg Vollmer
    Coley Pharmaceutical GmbH, Elisabeth Selbert Strasse 9, D 40764 Langenfeld, Germany
    Antimicrob Agents Chemother 48:2314-7. 2004
    ..CpG ODN represent a promising new type of therapeutic drug for hepatitis C or other infectious diseases...
  38. ncbi request reprint Modulation of CpG oligodeoxynucleotide-mediated immune stimulation by locked nucleic acid (LNA)
    Jorg Vollmer
    Coley Pharmaceutical Group, D 40764 Langenfeld, Germany
    Oligonucleotides 14:23-31. 2004
    ..These data indicate that increasing amounts of LNA residues in the flanks or substitutions of CpG nucleobases with LNA reduce or eliminate the immune stimulatory effects of CpG-containing phosphorothioate ODN...
  39. ncbi request reprint Biodistribution and metabolism of immunostimulatory oligodeoxynucleotide CPG 7909 in mouse and rat tissues following subcutaneous administration
    Bernhard O Noll
    Coley Pharmaceutical GmbH, Elisabeth Selbert Strasse 9, D 40764 Langenfeld, Germany
    Biochem Pharmacol 69:981-91. 2005
    ..Degradation of CPG 7909 in vivo occurred predominantly by 3'exonucleases with additional cleavage by endonucleases...
  40. ncbi request reprint Characterization of three CpG oligodeoxynucleotide classes with distinct immunostimulatory activities
    Jorg Vollmer
    Coley Pharmaceutical Group, Langenfeld, Germany
    Eur J Immunol 34:251-62. 2004
    ..In vivo studies demonstrate that C-Class ODN are very potent Th1 adjuvants. C-Class ODN may represent new therapeutic drugs that combine the effects of A- and B-Class ODN for broad applications in infectious disease or cancer therapy...
  41. doi request reprint Paclitaxel reduces regulatory T cell numbers and inhibitory function and enhances the anti-tumor effects of the TLR9 agonist PF-3512676 in the mouse
    Alain P Vicari
    Coley Pharmaceutical Group A Pfizer Company, 340 Terry Fox Drive, Suite 200, Ottawa, ON, K2K 3A2, Canada
    Cancer Immunol Immunother 58:615-28. 2009
    ....
  42. pmc Oligodeoxynucleotides lacking CpG dinucleotides mediate Toll-like receptor 9 dependent T helper type 2 biased immune stimulation
    Jorg Vollmer
    Coley Pharmaceutical, Langenfeld, Germany
    Immunology 113:212-23. 2004
    ..Our study indicates that TLR9 can mediate either efficient Th1- or Th2-dominated effects depending on whether it is stimulated by CpG or certain non-CpG ODN...
  43. ncbi request reprint Inhibitory oligonucleotides specifically block effects of stimulatory CpG oligonucleotides in B cells
    Laura L Stunz
    Department of Medicine, Iowa City Veterans Administration Medical Center, Iowa City, USA
    Eur J Immunol 32:1212-22. 2002
    ..Inhibitory ODN hold potential as antidotes for excessive ODN stimulation in the clinical setting and provide an important tool for studying ODN recognition...
  44. ncbi request reprint Antitumor mechanisms of oligodeoxynucleotides with CpG and polyG motifs in murine prostate cancer cells: decrease of NF-kappaB and AP-1 binding activities and induction of apoptosis
    Weiyin Shen
    Department of Internal Medicine, University of Iowa, Iowa City 52242, USA
    Antisense Nucleic Acid Drug Dev 12:155-64. 2002
    ..ODN containing both polyG and CpG motifs may have enhanced efficacy in tumor therapy through multiple mechanisms of action, including direct antitumor activities and immune activation...
  45. ncbi request reprint CpG oligonucleotides enhance the tumor antigen-specific immune response of a granulocyte macrophage colony-stimulating factor-based vaccine strategy in neuroblastoma
    Anthony D Sandler
    Department of Surgery, University of Iowa College of Medicine, Iowa City, Iowa 52246, USA
    Cancer Res 63:394-9. 2003
    ..This vaccine strategy elicits a potent tumor antigen-specific immune response against established murine neuroblastoma and generates systemic neuroblastoma-specific immunity...
  46. ncbi request reprint The role of CpG dinucleotides in DNA vaccines
    A M Krieg
    University of Iowa, Dept of Internal Medicine, Iowa City 52242, USA
    Trends Microbiol 6:23-7. 1998
    ..These CpG motifs can be added deliberately to DNA or conventional protein vaccines to enhance the Th1 immune response...
  47. ncbi request reprint The role of CpG motifs in innate immunity
    A M Krieg
    Department of Veterans Affairs Medical Center, Department of Internal Medicine, University of Iowa College of Medicine, Iowa City, IA 52242, USA
    Curr Opin Immunol 12:35-43. 2000
    ..Oligodeoxynucleotides containing CpG motifs are highly effective Th1-like vaccine adjuvants through multiple routes of immunization and show promise as immunotherapeutic agents for cancer and allergic diseases...
  48. ncbi request reprint Enhancing vaccines with immune stimulatory CpG DNA
    A M Krieg
    Department of Veterans Affairs Medical Center, Iowa City, IA 52246, USA
    Curr Opin Mol Ther 3:15-24. 2001
    ..The activity of CpG DNA can be mimicked with synthetic oligodeoxynucleotides, which when added to a vaccine greatly boost the resulting immune response...
  49. ncbi request reprint Mechanisms and applications of immune stimulatory CpG oligodeoxynucleotides
    A M Krieg
    Department of Veterans Affairs Medical Center, Iowa City, IA 52246, USA
    Biochim Biophys Acta 1489:107-16. 1999
    ....
  50. ncbi request reprint Lactoferrin binds CpG-containing oligonucleotides and inhibits their immunostimulatory effects on human B cells
    B E Britigan
    Research Service and Department of Internal Medicine, Veterans Affairs Medical Center, Iowa City, IA 52246, USA
    J Immunol 167:2921-8. 2001
    ..Lactoferrin binding of CpG-containing ODN may serve to modulate and terminate host response to these potent immunostimulatory molecules at mucosal surfaces and sites of bacterial infection...
  51. ncbi request reprint Immune effects and mechanisms of action of CpG motifs
    A M Krieg
    Department of Veterans Affairs Medical Center, Iowa City, IA 52246, USA
    Vaccine 19:618-22. 2000
    ..These responses can be mimicked using synthetic oligodeoxyribonucleotides, which have demonstrated remarkable utility as vaccine adjuvants and as immunotherapeutics for treatment of cancer and allergic diseases...
  52. ncbi request reprint Enhancement of infectious disease vaccines through TLR9-dependent recognition of CpG DNA
    M J McCluskie
    Coley Pharmaceutical Group, Inc, 93 Worcester Street, Suite 101, Wellesley, MA 02481, USA
    Curr Top Microbiol Immunol 311:155-78. 2006
    ..Used as vaccine adjuvants, synthetic oligodeoxynucleotide (ODN) ligands for TLR9--CpG ODN--greatly enhance the speed and strength of the immune responses to vaccination...
  53. ncbi request reprint Mechanisms and therapeutic applications of immune stimulatory cpG DNA
    A M Krieg
    Department of Internal Medicine and Interdisciplinary Immunology Program, University of Iowa, Iowa City 52242, USA
    Pharmacol Ther 84:113-20. 1999
    ..Animal studies indicate therapeutic utility for CpG-S DNA as a vaccine adjuvant and for the immunotherapy of cancer and infectious and allergic diseases...
  54. pmc Sequence motifs in adenoviral DNA block immune activation by stimulatory CpG motifs
    A M Krieg
    Interdisciplinary Immunology Program and Department of Internal Medicine, University of Iowa College of Medicine, Iowa City, IA 52242, USA
    Proc Natl Acad Sci U S A 95:12631-6. 1998
    ..These results have important implications for understanding microbial pathogenesis and molecular evolution and for the clinical development of DNA vaccines and gene therapy vectors...
  55. ncbi request reprint CpG DNA induces sustained IL-12 expression in vivo and resistance to Listeria monocytogenes challenge
    A M Krieg
    Interdisciplinary Graduate Program in Immunology, Department of Internal Medicine, University of Iowa, Iowa City 52242, USA
    J Immunol 161:2428-34. 1998
    ..These data support the hypothesis that CpG DNA motifs are a "danger signal" that activates protective innate immune defenses and may have therapeutic potential...
  56. ncbi request reprint Identification of methylated CpG motifs as inhibitors of the immune stimulatory CpG motifs
    Y Chen
    Department of Internal Medicine, University of Iowa, Iowa City, IA 52242, USA
    Gene Ther 8:1024-32. 2001
    ..Our results suggest that methylated DNA may be applied to alleviate the unwanted immune stimulation and inflammation in systemic inflammatory response syndrome and in gene therapy with plasmid DNA...
  57. pmc Immunostimulatory oligodeoxynucleotides containing the CpG motif are effective as immune adjuvants in tumor antigen immunization
    G J Weiner
    Department of Internal Medicine, University of Iowa, University of Iowa Cancer Center, University of Iowa Graduate Program in Immunology, and Iowa City Veterans Affairs Medical Center, Iowa City, IA 52242, USA
    Proc Natl Acad Sci U S A 94:10833-7. 1997
    ..We conclude that CpG ODN are effective as immune adjuvants and are attractive as part of a tumor immunization strategy...
  58. ncbi request reprint CpG DNA induces cyclooxygenase-2 expression and prostaglandin production
    Y Chen
    Department of Internal Medicine, University of Iowa College of Medicine, 200 Hawkins Drive, Iowa City, IA 52242, USA
    Int Immunol 13:1013-20. 2001
    ..Taken together, these data indicate that DNA containing CpG motifs is a potent inducer of COX-2 and PGE (2) production. CpG-induced PG may subsequently down-regulate the immune and inflammatory responses elicited by the CpG DNA...
  59. ncbi request reprint Divergent therapeutic and immunologic effects of oligodeoxynucleotides with distinct CpG motifs
    Z K Ballas
    Department of Veterans Affairs Medical Center, Iowa City, IA 52246, USA
    J Immunol 167:4878-86. 2001
    ....
  60. ncbi request reprint Direct immunologic activities of CpG DNA and implications for gene therapy
    A M Krieg
    Department of Veterans Affairs Medical Center, Iowa City, IA 52246, USA
    J Gene Med 1:56-63. 1999
    ..While this is useful in generating enhanced genetic vaccines, the opposite strategy is likely to become useful for the generation of gene therapy vectors with reduced inflammatory effects...
  61. pmc CpG motifs in bacterial DNA cause inflammation in the lower respiratory tract
    D A Schwartz
    Pulmonary, Critical Care, and Occupational Medicine Division, The University of Iowa, Iowa City, Iowa 52242, USA
    J Clin Invest 100:68-73. 1997
    ..These findings suggest that bacterial DNA, and unmethylated CpG motifs in particular, may play an important pathogenic role in inflammatory lung disease...
  62. ncbi request reprint CpG stimulation of primary mouse B cells is blocked by inhibitory oligodeoxyribonucleotides at a site proximal to NF-kappaB activation
    P Lenert
    Department of Internal Medicine, University of Iowa, College of Medicine, Iowa City 52242, USA
    Antisense Nucleic Acid Drug Dev 11:247-56. 2001
    ....
  63. ncbi request reprint Lymphocyte activation by CpG dinucleotide motifs in prokaryotic DNA
    A M Krieg
    Department of Internal Medicine, University of Iowa College of Medicine, Iowa City 52246, USA
    Trends Microbiol 4:73-6. 1996
    ..The vertebrate immune system has apparently evolved the ability to recognize these unmethylated CpG motifs and respond with a rapid and coordinated cytokine response leading to the induction of humoral and cell-mediated immunity...
  64. ncbi request reprint Type I interferon is the primary regulator of inducible Ly-6C expression on T cells
    A J Schlueter
    Department of Pathology, University of Iowa College of Medicine, Iowa City, IA 52242 1181, USA
    J Interferon Cytokine Res 21:621-9. 2001
    ..Thus, inducible Ly-6C expression on CD4+ and CD8+ T cells is largely due to IFN-alpha in the environment and appears not to be directly correlated with the development of T cell memory...
  65. ncbi request reprint Lymphoma immunotherapy with CpG oligodeoxynucleotides requires TLR9 either in the host or in the tumor itself
    Jiali Li
    Department of Medicine, Division of Oncology, Stanford University Medical Center, Stanford, CA 94305, USA
    J Immunol 179:2493-500. 2007
    ..These results indicate that activation of Ag presentation by cells within the tumor via TLR9 stimulation can be an effective form of immunotherapy. This study forms the basis of an ongoing clinical trial in patients with lymphoma...
  66. pmc CpG oligodeoxynucleotide and Montanide ISA 51 adjuvant combination enhanced the protective efficacy of a subunit malaria vaccine
    Sanjai Kumar
    Malaria Program, Naval Medical Research Center, Silver Spring, Maryland 20910, USA
    Infect Immun 72:949-57. 2004
    ..Our results indicate that this potent adjuvant formulation should be further evaluated for use in clinical trials of recombinant malarial vaccine candidates...
  67. ncbi request reprint Dendritic cells pulsed or fused with AML cellular antigen provide comparable in vivo antitumor protective responses
    Brenda J Weigel
    University of Minnesota Cancer Center and Department of Pediatrics, Division of Pediatric Hematology Oncology and Blood and Marrow Transplant, Minneapolis, MN 55455, USA
    Exp Hematol 34:1403-12. 2006
    ....
  68. pmc Activation of innate immunity in healthy Macaca mulatta macaques by a single subcutaneous dose of GMP CpG 7909: safety data and interferon-inducible protein-10 kinetics for humans and macaques
    V Ann Stewart
    Walter Reed Army Institute of Research, Silver Spring, Maryland, USA
    Clin Vaccine Immunol 15:221-6. 2008
    ....
  69. ncbi request reprint Identification of RNA sequence motifs stimulating sequence-specific TLR8-dependent immune responses
    Alexandra Forsbach
    Coley Pharmaceutical GmbH, Dusseldorf, Germany
    J Immunol 180:3729-38. 2008
    ..In summary, we describe two classes of single-stranded TLR7/8 and TLR8 RNA agonists with diverse target cell and species specificities and immune response profiles...
  70. pmc A combination of Flt3 ligand cDNA and CpG ODN as nasal adjuvant elicits NALT dendritic cells for prolonged mucosal immunity
    Tatsuya Fukuiwa
    The Immunobiology Vaccine Center, Department of Pediatric Dentistry, The University of Alabama at Birmingham, Birmingham, AL 35294 0007, USA
    Vaccine 26:4849-59. 2008
    ..These results demonstrate that nasal delivery of a combined DNA adjuvant offers an attractive possibility for the development of an effective mucosal vaccine for the elderly...
  71. ncbi request reprint Comparative analysis of murine marrow-derived dendritic cells generated by Flt3L or GM-CSF/IL-4 and matured with immune stimulatory agents on the in vivo induction of antileukemia responses
    Brenda J Weigel
    University of Minnesota Cancer Center and Department of Pediatrics, Division of Pediatric Hematology Oncology and Blood and Marrow Transplant, Minneapolis 55455, USA
    Blood 100:4169-76. 2002
    ..These data have important clinical implications and are the first to show that Flt3L-generated DCs can provide antitumor protection and that nontoxic agents such as CpGs and Flt3L may be useful in the clinical development of DC vaccines...
  72. ncbi request reprint CpG oligodeoxynucleotides stimulate IFN-gamma-inducible protein-10 production in human B cells
    Jorg Vollmer
    Coley Pharmaceutical GmbH, Langenfeld, Germany
    J Endotoxin Res 10:431-8. 2004
    ..Our data provide a better understanding of the mechanisms through which CpG ODNs induce efficient Th1 responses...
  73. ncbi request reprint TLR9 and DNA 'feel' RAGE
    Arthur M Krieg
    Nat Immunol 8:475-7. 2007
  74. pmc Impact of class A, B and C CpG-oligodeoxynucleotides on in vitro activation of innate immune cells in human immunodeficiency virus-1 infected individuals
    Jeffrey A Martinson
    Department of Immunology Microbiology, Rush University Medical Center, Chicago, IL 60612, USA
    Immunology 120:526-35. 2007
    ....
  75. ncbi request reprint Comparison of CpG s-ODNs, chromatin immune complexes, and dsDNA fragment immune complexes in the TLR9-dependent activation of rheumatoid factor B cells
    Ann Marshak-Rothstein
    Department of Microbiology, Boston University School of Medicine, Boston, Massachusetts, USA
    J Endotoxin Res 10:247-51. 2004
    ..These data have important implications regarding the therapeutic application of TLR9 inhibitors to the treatment of systemic autoimmune diseases...
  76. ncbi request reprint Convergence of CpG DNA- and BCR-mediated signals at the c-Jun N-terminal kinase and NF-kappaB activation pathways: regulation by mitogen-activated protein kinases
    Ae Kyung Yi
    Children s Foundation Research Center at Le Bonheur Children s Medical Center, Department of Pediatrics, University of Tennessee Health Science Center, Memphis, TN 38103, USA
    Int Immunol 15:577-91. 2003
    ....
  77. ncbi request reprint Human plasmacytoid dendritic cells activated by CpG oligodeoxynucleotides induce the generation of CD4+CD25+ regulatory T cells
    E Ashley Moseman
    University of Minnesota Cancer Center and Department of Pediatrics, and Division of Hematology, Oncology, and Bone Marrow Transplantation, Minneapolis, MN 55455, USA
    J Immunol 173:4433-42. 2004
    ..This study demonstrates that TLR9 stimulation can promote PDC-mediated generation of CD4(+)CD25(+) Treg cells and suggests PDCs may play an important role in the maintenance of immunological tolerance...
  78. ncbi request reprint A role for Toll in autoimmunity
    Arthur M Krieg
    Nat Immunol 3:423-4. 2002
  79. ncbi request reprint Stimulation via Toll-like receptor 9 reduces Cryptococcus neoformans-induced pulmonary inflammation in an IL-12-dependent manner
    Lorna Edwards
    Department of Biological Sciences, Imperial College London, CMMI, London SW7 2AZ, UK
    Eur J Immunol 35:273-81. 2005
    ..Activation of innate immunity has clear therapeutic potential and may even be beneficial in patients with acquired immune deficiency...
  80. ncbi request reprint Targeting toll-like receptor 9 with CpG oligodeoxynucleotides enhances tumor response to fractionated radiotherapy
    Kathryn A Mason
    Department of Experimental Radiation Oncology, University of Texas M D Anderson Cancer Center, Houston, Texas 77030 4009, USA
    Clin Cancer Res 11:361-9. 2005
    ..c. and i.t., respectively. These findings show that CpG oligodeoxynucleotides are highly potent enhancers of tumor response to both single-dose and fractionated radiation and as such have potential to improve clinical radiotherapy...
  81. ncbi request reprint Malaria blood stage parasites activate human plasmacytoid dendritic cells and murine dendritic cells through a Toll-like receptor 9-dependent pathway
    Sathit Pichyangkul
    Department of Immunology and Medicine, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand
    J Immunol 172:4926-33. 2004
    ....
  82. pmc Deoxycytidyl-deoxyguanosine oligonucleotide classes A, B, and C induce distinct cytokine gene expression patterns in rhesus monkey peripheral blood mononuclear cells and distinct alpha interferon responses in TLR9-expressing rhesus monkey plasmacytoid den
    Kristina Abel
    Center for Comparative Medicine, University of California Davis, CA 95616, USA
    Clin Diagn Lab Immunol 12:606-21. 2005
    ..Based on these findings, A and C class CpG ODN, but not B class CpG ODN, may be particularly suited for use as therapeutic or prophylactic antiviral interventions...
  83. ncbi request reprint Human TLR7 or TLR8 independently confer responsiveness to the antiviral compound R-848
    Marion Jurk
    Nat Immunol 3:499. 2002
  84. ncbi request reprint Activation of plasmacytoid dendritic cells with TLR9 agonists initiates invariant NKT cell-mediated cross-talk with myeloid dendritic cells
    Carlos J Montoya
    Department of Immunology and Microbiology, Rush University Medical Center, Chicago, IL 60612, USA
    J Immunol 177:1028-39. 2006
    ..This interaction supports the notion that iNKT cells can mediate cross-talk between DC subsets known to express mutually exclusive TLR and cytokine profiles...
  85. ncbi request reprint Decreased cytotoxic T cell activity generated by co-administration of PSA vaccine and CpG ODN is associated with increased tumor protection in a mouse model of prostate cancer
    David M Lubaroff
    Department of Urology, 375 Newton Road, 3210 MERF, The University of Iowa, Iowa City, IA, United States
    Vaccine 24:6155-62. 2006
    ....
  86. ncbi request reprint Structure-activity relationship studies on the immune stimulatory effects of base-modified CpG toll-like receptor 9 agonists
    Marion Jurk
    Coley Pharmaceutical GmbH, Elisabeth Selbert Strasse 9, 40764 Langenfeld, Germany
    ChemMedChem 1:1007-14. 2006
    ..In addition, we found significant species-specific differences between human and murine TLR9 recognition, which demonstrates the importance of choosing appropriate assay systems for SAR studies...
  87. ncbi request reprint Role of mitogen-activated protein kinases in CpG DNA-mediated IL-10 and IL-12 production: central role of extracellular signal-regulated kinase in the negative feedback loop of the CpG DNA-mediated Th1 response
    Ae Kyung Yi
    Children s Foundation Research Center, Le Bonheur Children s Hospital, and Department of Pediatrics, University of Tennessee Health Science Center, Memphis, TN 38103, USA
    J Immunol 168:4711-20. 2002
    ..In contrast, ERK plays a central negative regulatory role in the CpG DNA-mediated Th1 type response by promoting production of the Th2 type cytokine, IL-10...
  88. ncbi request reprint Innate immune responses induced by classes of CpG oligodeoxynucleotides in ovine lymph node and blood mononuclear cells
    Jayaum S Booth
    Vaccine and Infectious Disease Organization, University of Saskatchewan, 120 Veterinary Road, Saskatoon, Sask, Canada S7N 5E3
    Vet Immunol Immunopathol 115:24-34. 2007
    ....
  89. ncbi request reprint High mobility group B1 protein suppresses the human plasmacytoid dendritic cell response to TLR9 agonists
    Petar J Popovic
    Division of Surgical Oncology, Department of Surgery and Molecular Medicine Institute, University of Pittsburgh, Pittsburgh, PA 15232, USA
    J Immunol 177:8701-7. 2006
    ..Our observations suggest that HMGB1 may play a critical role in regulating the immune response during chronic inflammation and tissue damage through modulation of PDC function...
  90. pmc Immunostimulatory CpG oligodeoxynucleotide confers protection in a murine model of infection with Burkholderia pseudomallei
    Surasakdi Wongratanacheewin
    Department of Microbiology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand
    Infect Immun 72:4494-502. 2004
    ..pseudomallei multiplication...