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Review

Progress in drug development of immunostimulatory CpG oligodeoxynucleotide ligands for TLR9

Pages 673-682 | Published online: 24 Nov 2005

Bibliography

  • IWASAKI A, MEDZHITOV R: Toll-like receptor control of the adaptive immune responses. Nat. Immunol (2004) 5:987–995.
  • •Review to summarise current knowledge on TLRs.
  • PEISER L, MUKHOPADHYAY S, GORDON S: Scavenger receptors in innate immunity. Curr. Opin. Immunol (2002) 14:123–128.
  • MARTINEZ-POMARES L, LINEHAN SA, TAYLOR PR, GORDON S: Binding properties of the mannose receptor. Immunobiology (2001) 204:527–535.
  • HERRE J, GORDON S, BROWN GD: Dectin-1 and its role in the recognition of beta-glucans by macrophages.
  • MoL Immunol (2004) 40:869–876.
  • TAKEDA K, KAISHO T, AKIRA S: Toll-like receptors. Annu. Rev. Immunol (2003) 21:335–376.
  • HEIL F, HEMMI H, HOCHREIN H et al.: Species-specific recognition of single-stranded RNA via toll-like receptor 7 and 8. Science (2004) 303:1526–1529.
  • •Establishes that RNA is a ligand for TLR7 and 8.
  • DIEBOLD SS, KAISHO T, HEMMI H, AKIRA S, REIS E SOUSA: Innate antiviral responses by means of TLR7-mediated recognition of single-stranded RNA. Science (2004) 303:1529–1531.
  • •Establishes that RNA is a ligand for TLR7 and 8.
  • HEMMI H, TAKEUCHI O, KAWAI T et al.: A Toll-like receptor recognizes bacterial DNA. Nature (2000) 408:740–745.
  • ••Identifies TLR9 as the receptor forCpG DNA.
  • KRUG A, FRENCH AR, BARCHET W et al.: TLR9-dependent recognition of MCMV by IPC and DC generates coordinated cytokine responses that activate antiviral NK cell function. Immunity (2004) 21:107–119.
  • HOCHREIN H, SCHLATTER B, O'KEEFFE M et al.: Herpes simplex virus type-1 induces IFN-alpha production via Toll-like receptor 9-dependent and - independent pathways. Proc. Natl Acad. Sci. USA (2004) 101:11416–11421.
  • TABETA K, GEORGEL P, JANSSEN E et al.: Toll-like receptors 9 and 3 as essential components of innate immune defense against mouse cytomegalovirus infection. Proc. Nail. Acad. Sci. USA (2004) 101:3516–3521.
  • KRIEG AM: CpG motifs in bacterial DNA and their immune effects. Annu. Rev. Immunol (2002) 20:709–760.
  • UHLMANN E, VOLLMER J: Recent advances in the development of immunostimulatory oligonucleotides. Curr. Opin. Drug Discov. Devel (2003) 6:204–217.
  • •Gives an overview on stimulation and chemical modification of CpG ODNs.
  • HARTMANN G, KRIEG AM: Mechanism and function of a newly identified CpG DNA motif in human primary B cells. J. Immunol (2000) 164:944–953.
  • KRIEG AM, YT AK, MATSON S et al.: CpG motifs in bacterial DNA trigger direct B-cell activation. Nature (1995) 374:546–549.
  • RUTZ M, METZGER J, GELLERT T et al.: Toll-like receptor 9 binds single-stranded CpG-DNA in a sequence- and pH-dependent manner. Eur. j Immunol (2004) 34:2541–2550.
  • ••Describes the direct binding of CpG ODNs to the human and murine TLR9 proteins.
  • LATZ E, SCHOENEMEYER A, VISINTIN A et al.: TLR9 signals after translocating from the ER to CpG DNA in the lysosome. Nat. Immunol. (2004).
  • •Describes the recruitment of TLR9 from the ER to sites of CpG DNA uptake, where signal transduction is initiated.
  • AHMAD-NEJAD P, HACKER H, RUTZ M et al.: Bacterial CpG-DNA and lipopolysaccharides activate Toll-like receptors at distinct cellular compartments. Eur. J. Immunol (2002) 32:1958–1968.
  • SCHETTER C, VOLLMER J: Toll-like receptors involved in the response to microbial pathogens:Development of agonists for toll-like receptor 9. Curr. Opin. Drug Discov. Devel (2004) 7:204–210.
  • PLATZ J, BEISSWENGER C, DALPKE A et al.: Microbial DNA induces a host defense reaction of human respiratory epithelial cells. J. Immunol. (2004) 173:1219–1223.
  • LI J, MA Z, TANG ZL et al.: CpG DNA-mediated immune response in pulmonary endothelial cells. Am. J. PhysioL Lung Cell
  • Mol Physiol. (2004) 287:L552–L558.
  • TREVANI AS, CHORNY A, SALAMONE G et al.: Bacterial DNA activates human neutrophils by a CpG-independent pathway. Eur. Immunol (2003) 33:3164–3174.
  • VOLLMER J, WEERATNA R, PAYETTE P et al.: Characterization of three CpG oligodeoxynucleotide classes with distinct immunostimulatory activities. Eur. j Immunol (2004) 34:251–262.
  • •Compares the immunomodulatory activities of the CpG A-, B- and C-classes on human and murine immune cells.
  • KRUG A, ROTHENFUSSER S, SELINGER S et al.: CpG-A oligonucleotides induce a monocyte-derived dendritic cell-like phenotype that preferentially activates CD8 T cells. Immunol (2003) 170:3468–3477.
  • GURSEL M, VERTHELYI D, KLINMAN DM: CpG oligodeoxynucleotides induce human monocytes to mature into functional dendritic cells. Eur. J. Immunol (2002) 32:2617–2622.
  • KEMP TJ, ELZEY BD, GRIFFITH TS: Plasmacytoid dendritic cell-derived IFN-alpha induces TNF-related apoptosis-inducing ligand/Apo-2L-mediated antitumor activity by human monocytes following CpG oligodeoxynucleotide stimulation. J. Immunol (2003) 171:212–218.
  • POECK H, WAGNER M, BATTIANY J et al.: Plasmacytoid dendritic cells, antigen, and CpG-C license human B cells for plasma cell differentiation and immunoglobulin production in the absence of T-cell help. Blood (2004) 103:3058–3064.
  • OLSON JK, MILLER SD: Microglia initiate central nervous system innate and adaptive immune responses through multiple TLRs. J. Immunol (2004) 173:3916–3924.
  • BOWMAN CC, RASLEY A. TRANGUCH SL, MARRIOTT I: Cultured astrocytes express toll-like receptors for bacterial products. GYM (2003) 43:281–291.
  • BARTON GM, MEDZHITOV R: Toll-like receptor signaling pathways. Science (2003) 300:1524–1525.
  • TSUJIMURA H, TAMURA T, KONG HJ et al.: Toll-like receptor 9 signaling activates NF-kappaB through IFN regulatory factor-8/IFN consensus sequence binding protein in dendritic cells. J. Immunol (2004) 172:6820–6827.
  • LIU N, OHNISHI N, NI L, AKIRA S, BACON KB: CpG directly induces T-bet expression and inhibits IgG1 and IgE switching in B cells. Nat. Immunol (2003) 4:687–693.
  • JEFFERIES CA, DOYLE S, BRUNNER C et al.: Bruton's tyrosine kinase is a Toll/ interleukin-1 receptor domain-binding protein that participates in nuclear factor fkappalB activation by Toll-like receptor 4. J. Biol Chem. (2003) 278:26258–26264.
  • KAWAI T, SATO S, ISHII KJ et al.: Interferon-alpha induction through Toll-like receptors involves a direct interaction of IRF7 with MyD88 and TRAF6. Nat. Immunol (2004).
  • •Establishes that type I IFN stimulation via T1129 involves complex formation between different signalling molecules.
  • HONDA K, YANAI H, MIZUTANI T et al.: Role of a transductional-transcriptional processor complex involving MyD88 and IRF-7 in Toll-like receptor signaling. Proc. Natl Acad. Sci. USA (2004) 101:15416–15421.
  • •Establishes that type I IFN stimulation via T1129 involves complex formation between different signalling molecules.
  • VOLLMER J, JURK M, SAMULOWITZ U et al.: CpG oligodeoxynucleotides stimulate IFN-gamma-inducible protein-10 production in human B cells. J. Endotoxin Res. (2004) 10:431–438.
  • KRUG A. ROTHENFUSSER S, HORNUNG Vet al.: Identification of CpG oligonucleotide sequences with high induction of IFN-alpha/beta in plasmacytoid dendritic cells. Eur. J. Immunol (2001) 31:2154–2163.
  • JURK M, SCHULTE B, KRITZLER A et al.: C-Class CpG ODN: sequence requirements and characterization of immunostimulatory activities on mRNA level. immunobidogy (2004) 209:141–154.
  • MARSHALL JD, FEARON K, ABBATE C et al.: Identification of a novel CpG DNA class and motif that optimally stimulate B cell and plasmacytoid dendritic cell functions. J. Leukoc. Biol (2003) 73:781–792.
  • HARTMANN G, BATTIANY J, POECK H et al.: Rational design of new CpG oligonucleotides that combine B cell activation with high IFN-A induction in plasmacytoid dendritic cells. Eur. Immunol (2003) 33:1633–1641.
  • VOLLMER J, WEERATNA RD, JURK M et al.: Impact of modifications of heterocyclic bases in CpG dinucleotides on their immune-modulatory activity. Leukoc. Biol. (2004) 76:585–593.
  • KANDIMALLA ER, BHAGAT L, WANG D et al.: Divergent synthetic nucleotide motif recognition pattern: design and development of potent immunomodulatory oligodeoxyribonucleotide agents with distinct cytokine induction profiles. Nucleic Acids Res. (2003) 31:2393–2400.
  • KANDIMALLA ER, YU D, ZHAO Q, AGRAWAL S: Effect of chemical modifications of cytosine and guanine in a CpG-motif of oligonucleotides: structure-immunostimulatory activity relationships. Bioorg Med. Chem. (2001) 9:807–813.
  • VOLLMER J, JEPSEN JS, UHLMANN Eet al.: Modulation of CpG oligodeoxynucleotide-mediated immune stimulation by locked nucleic acid (LNA). Oligonucleotides (2004) 14:23–31.
  • VOLLMER J, WEERATNA RD, JURK M et al.: Oligodeoxynucleotides lacking CpG dinucleotides mediate Toll-like receptor 9 dependent T helper type 2 biased immune stimulation. Immunology (2004) 113:212–223.
  • ELIAS F, FLO J, LOPEZ RA et al.: Strongcytosine-guanosine-independent immunostimulation in humans and other primates by synthetic oligodeoxynucleotides with PyNTTTTGT motifs. J. Immunol (2003) 171:3697–3704.
  • VOLLMER J, JANOSCH A, LAUCHT M et al.: Highly immunostimulatory CpG-free oligodeoxynucleotides for activation of human leukocytes. Antisense Nucleic Acid Drug Dev. (2002) 12:165–175.
  • ZHAO Q, YU D, AGRAWAL S: Immunostimulatory activity of CpG containing phosphorothioate oligodeoxynucleotide is modulated by modification of a single deoxynucleoside. Bioorg. Med. Chem. Lett. (2000) 10:1051–1054.
  • YASUDA K, OGAWA Y, YAIVIANE I, NISHIKAWA M, TAKAKURA Y: Macrophage activation by a DNA/cationic liposome complex requires endosomal acidification and TLR9-dependent and -independent pathways. J. Leukoc. Biol. (2005) 77:71–79.
  • ZHU FG, REICH CF, PISETSKY DS: Effect of cytofectins on the immune response of murine macrophages to mammalian DNA. Immunology (2003) 109:255–262.
  • LENERT P, STUNZ L, YT AK, KRIEG AM, ASHMAN RF: CpG stimulation of primary mouse B cells is blocked by inhibitory oligodeoxyribonucleotides at a site proximal to NF-kappaB activation. Antisense Nucleic Acid Drug Dev. (2001) 11:247–256.
  • LENERT P, RASMUSSEN W, ASHMAN RF, BALLAS ZK: Structural characterization of the inhibitory DNA motif for the type A (D)-CpG-induced cytokine secretion and NK-cell lytic activity in mouse spleen cells. DNA Cell Biol. (2003) 22:621–631.
  • STUNZ LL, LENERT P, PECKHAM D et al.: Inhibitory oligonucleotides specifically block effects of stimulatory CpG oligonucleotides in B cells. Eur. j Immunol (2002) 32:1212–1222.
  • LEADBETTER EA, RIFKIN IR, HOHLBAUM AM et al.: Chromatin-IgG complexes activate B cells by dual engagement of IgM and Toll-like receptors. Nature (2002) 416:603–607.
  • DONG L, ITO S, ISHII KJ, KLINMAN DM: Suppressive oligodeoxynucleotides delay the onset of glomerulonephritis and prolong survival in lupus-prone NZB x NZW mice. Arthritis Rheum. (2005) 52:651–658.
  • •Demonstrates that inhibitory S-class ODNs can be used to treat autoimmune diseases in an animal model.
  • DONG L, ITO S, ISHII KJ, KLINMAN DM: Suppressive oligonucleotides protect against collagen-induced arthritis in mice. Arthritis Rheum. (2004) 50:1686–1689.
  • •Demonstrates that inhibitory S-class ODNs can be used to treat autoimmune diseases in an animal model.
  • KRIEG AM: CpG motifs: the active ingredient in bacterial extracts? Nat. Med. (2003) 9:831–835.
  • JAHRSDORFER B, WEINER GJ: CpG oligodeoxynucleotides for immune stimulation in cancer immunotherapy. Curr. Opin. Investig. Drugs (2003) 4:686–690.
  • CARPENTIER AF, AUF G, DELATTRE JY: CpG-oligonucleotides for cancer immunotherapy: review of the literature and potential applications in malignant glioma. Front. Biosci. (2003) 8:e115–e127.
  • BAINES J, CELTS E: Immune-mediated tumor regression induced by CpG-containing oligodeoxynucleotides. Clin. Cancer Res. (2003) 9:2693–2700.
  • HECKELSMILLER K, RALL K, BECK S et al.: Peritumoral CpG DNA elicits a coordinated response of CD8 T cells and innate effectors to cure established tumors in a murine colon carcinoma model. Immunol (2002) 169:3892–3899.
  • KAWARADA Y, GANSS R, GARBI N et al.: NK- and CD8(+) T cell-mediated eradication of established tumors by peritumoral injection of CpG-containing oligodeoxynucleotides. j Immunol (2001) 167:5247–5253.
  • JAHRSDORFER B, WEINER GJ: Immunostimulatory CpG oligodeoxynucleotides and antibody therapy of cancer. Semin. Oncol (2003) 30:476–482.
  • JAHRSDORFER B, HARTMANN G, RACILA E et al.: CpG DNA increases primary malignant B cell expression of costimulatory molecules and target antigens./ Leukoc. Biol. (2001) 69:81–88.
  • •Describes the effects of CpG ODNs on TLR9-expressing tumour cells that may lead to an efficient antitumour effect.
  • HARTMANN E, WOLLENBERG B, ROTHENFUSSER S et al.: Identification and functional analysis of tumor-infiltrating plasmacytoid dendritic cells in head and neck cancer. Cancer Res. (2003) 63:6478–6487.
  • JAHRSDORFER B, WOOLDRIDGE JE, BLACKWELL SE et al.: Immunostimulatory oligodeoxynucleotides induce apoptosis of B cell chronic lymphocytic leukemia cells. J. Leukoc. Biol (2004) 77:378–387.
  • WEIGEL BJ, RODEBERG DA, KRIEG AM, BLAZAR BR: CpG oligodeoxynucleotides potentiate the antitumor effects of chemotherapy or tumor resection in an orthotopic murine model of rhabdomyosarcoma. Clin. Cancer Res. (2003) 9:3105–3114.
  • •CpG ODNs are demonstrated to enhance the activity of chemotherapy.
  • WARREN TL, WEINER GJ: Synergism between cytosine-guanine oligodeoxynucleotides and monoclonal antibody in the treatment of lymphoma. Semin. Oncol (2002) 29:93–97.
  • MILAS L, MASON KA, ARIGA H et al.: CpG oligodeoxynucleotide enhances tumor response to radiation. Cancer Res. (2004) 64:5074–5077.
  • •Describes that CpG ODNs enhance tumour growth delay in response to single-dose radiation.
  • ZWAVELING S, FERREIRA MOTA SC, NOUTA J et al.: Established human papillomavirus type 16-expressing tumors are effectively eradicated following vaccination with long peptides. J. Immunol (2002) 169:350–358.
  • HECKELSMILLER K, BECK S, RALL K et al.: Combined dendritic cell- and CpG oligonucleotide-based immune therapy cures large murine tumors that resist chemotherapy. Eur. J. Immunol (2002) 32:3235–3245.
  • MICONNET I, KOENIG S, SPEISER D et al.: CpG are efficient adjuvants for specific CTL induction against tumor antigen-derived peptide./ Immunol (2002) 168:1212–1218.
  • KIM TY, MYOUNG HJ, KIM JH et al.:Both E7 and CpG-oligodeoxynucleotide are required for protective immunity against challenge with human papillomavirus 16 (E6/E7) immortalized tumor cells: involvement of CD4+ and CD8+ T cells in protection. Cancer Res. (2002) 62:7234–7240.
  • DAVILA E, CELTS E: Repeated administration of cytosine-phosphorothiolated guanine-containing oligonucleotides together with peptide/ protein immunization results in enhanced CTL responses with anti-tumor activity. J. Immunol (2000) 165:539–547.
  • KLINE JN: Effects of CpG DNA on Thl /Th2 balance in asthma. Curr. Top. Microbiol Immunol (2000) 247:211–225.
  • KLINE JN, KRIEG AM, WALDSCHMIDT TJ et al: CpG oligodeoxynucleotides do not require TH1 cytokines to prevent eosinophilic airway inflammation in a murine model of asthma. J. Allergy Clin. Immunol (1999) 104:1258–1264.
  • VOLLMER J, RANKIN R, HARTMANN H et al: Immunopharmacology of CpG oligodeoxynucleotides and ribavirin. Antimicrob. Agents Chemother. (2004) 48:2314–2317.
  • BROIDE D, SCHWARZE J, TIGHE H et al.: Immunostimulatory DNA sequences inhibit IL-5, eosinophilic inflammation, and airway hyperresponsiveness in mice. Immunol (1998) 161:7054–7062.
  • SUR S, WILD JS, CHOUDHURY BK et al: Long term prevention of allergic lung inflammation in a mouse model of asthma by CpG oligodeoxynucleotides. J. Immunol (1999) 162:6284–6293.
  • JAIN VV, KITAGAKI K, KLINE JN: CpG DNA and immunotherapy of allergic airway diseases. Clin. Exp. Allergy (2003) 33:1330–1335.
  • SANTELIZ JV, VAN NEST G, TRAQUINA P, LARSEN E, WILLS-KARP M: Amb a 1-linked CpG oligodeoxynucleotides reverse established airway hyperresponsiveness in a murine model of asthma. J. Allergy Clin. Immunol (2002) 109:455–462.
  • SHIROTA H, SANO K, KIKUCHI T, TAMURA G, SHIRATO K: Regulation of T-helper Type 2 cell and airway eosinophilia by transmucosal coadministration of antigen and oligodeoxynucleotides containing CpG motifs. Am. J. Respir. Cell Mol Biol. (2000) 22:176–182.
  • SHIROTA H, SANO K, KIKUCHI T, TAMURA G, SHIRATO K: Regulation of murine airway eosinophilia and Th2 cells by antigen-conjugated CpG oligodeoxynucleotides as a novel antigen-specific immunomodulator. J. Immunol (2000) 164:5575–5582.
  • KLINE JN, KITAGAKI K, BUSINGA TR, JAIN VV: Treatment of established asthma in a murine model using CpG oligodeoxynucleotides. Am. J. Physiol Lung Cell Mot Physiol (2002) 283:L170–L179.
  • JAIN VV, KITAGAKI K, BUSINGA T et al.: CpG-oligodeoxynucleotides inhibit airway remodeling in a murine model of chronic asthma. J. Allergy Clin. Immunol (2002) 110:867–872.
  • KLINMAN DM: Use of CpG oligodeoxynucleotides as immunoprotective agents. Expert Opin. Biol. Ther. (2004) 4:937–946.
  • KIM SK, RAGUPATHI G, MUSSELLI C et al: Comparison of the effect of different immunological adjuvants on the antibody and T-cell response to immunization with MUC1-KLH and GD3-KLH conjugate cancer vaccines. Vaccine (1999) 18:597–603.
  • WEERATNA R, COMANITA L, DAVIS HL: CPG ODN allows lower dose of antigen against hepatitis B surface antigen in BALB/c mice. Immunol Cell Biol. (2003) 81:59–62.
  • HARTMANN G, WEERATNA RD, BALLAS ZK et al.: Delineation of a CpG phosphorothioate oligodeoxynucleotide for activating primate immune responses in vitro and in vivo. J. Immunol (2000) 164:1617–1624.
  • JONES TR, OBALDIA N GRAMZINSKI RA et al.: Synthetic oligodeoxynucleotides containing CpG motifs enhance immunogenicity of a peptide malaria vaccine in Aotus monkeys. Vaccine (1999) 17:3065–3071.
  • DAVIS HL, SUPARTO II, WEERATNA RR et al.: CpG DNA overcomes hyporesponsiveness to hepatitis B vaccine in orangutans. Vaccine (2000) 18:1920–1924.
  • KRIEG AM, LOVE-HOMAN L, YT AK, HARTY JT: CpG DNA induces sustained IL-12 expression in vivo and resistance to Listeria monocytogenes challenge. J. immund (1998) 161:2428–2434.
  • ZIMMERMANN S, EGETER O, HAUSMANN S et al.: CpG oligodeoxynucleotides trigger protective and curative Thl responses in lethal murine leishmaniasis. J. Immunol (1998) 160:3627–3630.
  • VERTHELYI D, GURSEL M, KENNEY RT et al.: CpG oligodeoxynucleotides protect normal and SIV-infected macaques from Leishmania infection. J. Immunol (2003) 170:4717–4723.
  • KRIEG AM, EFLER SM, WITTPOTH M, AL ADHAMI MJ, DAVIS HL: 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. J. Immunother. (2004) 27:460–471.
  • ••Original paper describing innate immuneeffects induced by CpG ODNs following injection in normal human volunteers.
  • FRIEDBERG P:(1, KIM H, MCCAULEY M et al.: Combination immunotherapy with a CpG oligonucleotide (1018 ISS) and rituximab in patients with non-Hodgkin's lymphoma: increased interferon-{alpha}/{beta}-inducible gene expression, without significant toxicity. Blood (2004) 105:489–495.
  • HEIKENWALDER M, POLYMENIDOU M, JUNT T et al: Lymphoid follicle destruction and immunosuppression after repeated CpG oligodeoxynucleotide administration. Nat. Med. (2004) 10:178–192.
  • SPARWASSER T, HULTNER L, KOCH ES et al.: Immunostimulatory CpG-oligodeoxynucleotides cause extramedullary murine hemopoiesis. Immunol (1999) 162:2368–2374.
  • COOPER CL, DAVIS HL, MORRIS ML et al.: CPG 7909, an immunostimulatory TLR9 agonist oligodeoxynucleotide, as adjuvant to Engerix-B HBV vaccine in healthy adults: a double-blind Phase I/II study./ Clin. Immunol (2004) 24:693–701.
  • •Describes the effect of a CpG ODN as an adjuvant to the HBV vaccine Engerix-B in healthy volunteers.
  • HALPERIN SA, VAN NEST G, SMITH B et al.: A Phase I study of the safety and immunogenicity of recombinant hepatitis B surface antigen co-administered with an immunostimulatory phosphorothioate oligonucleotide adjuvant. Vaccine (2003) 21:2461–2467.
  • •Describes the effect of a CpG ODN as an adjuvant to the HBV vaccine Engerix-B in healthy volunteers.
  • SIEGRIST CA, PIHLGREN M, TOUGNE C et al.: Co-administration of CpG oligonucleotides enhances the late affinity maturation process of human anti-hepatitis B vaccine response. Vaccine (2004) 23:615–622.
  • EVANS TG, HASAN M, GAUBERT L, CARON D: The use of F1t3 ligand as an adjuvant for hepatitis B vaccination of healthy adults. Vaccine (2002) 21:322–329.
  • HASAN MS, AGOSTI JM, REYNOLDS KK et al.: Granulocyte macrophage colony-stimulating factor as an adjuvant for hepatitis B vaccination of healthy adults. J. Infect. Dis. (1999) 180:2023–2026.
  • WEST DJ: Clinical experience with hepatitis B vaccines. Am. J. Infect. Control (1989) 17:172–180.
  • COOPER CL, DAVIS HL, MORRIS ML et al.: Safety and immunogenicity of CPG 7909 injection as an adjuvant to Fluarix influenza vaccine. Vaccine (2004) 22:3136–3143.
  • PAUL S: Technology evaluation: CpG-7909, Coley. Curr. Opin. Mol Ther. (2003) 5:553–559.
  • PASHENKOV M, GORSS G, WAGNER C et al.: Clinical and immunological activity of Toll-like receptor 9-targeting CpG oligodeoxynucleotide-based immunotherapy of metastatic melanoma. Submitted (2005).
  • BELARDELLI F, FERRANTINI M, PARMIANI G, SCHLOM J, GARACI E: International meeting on cancer vaccines: how can we enhance efficacy of therapeutic vaccines? Cancer Res. (2004) 64:6827–6830.
  • SCHMALBACH T, EFLER S, MORRIS ML et al.: CpG 10101 (Actilon) oligodeoxynucleotide TLR9 agonist: pharmacokinetics and pharmacodynamics in normal volunteers. Interscience Conference on Antimicrobial Agents and Chemotherapy (2004).
  • HWANG JJ, MARTIN R, FOX-SINCLAIR ES et al.: A Phase I study of a second generation immunomodulatory oligonucleotide (Hyb2055) in patients with solid malignancies. Clin. Cancer Res. (2003) 9:C111.
  • PICHARDO DA, QUERFELD C, GUITART J, KUZEL TM, ROSEN ST: Cutaneous T-cell lymphoma: a paradigm for biological therapies. Leuk. Lymphoma (2004) 45:1755–1765.
  • NO AUTHORS LISTED: Immunostimulatory DNA-Dynavax. AIC, Arnb a 1 immunostimulatory conjugate, HBV-ISS, ISS 1018, ISS DNA, ISS DNA-dynavax, ISS1, ISS2. Drugs RD (2002) 3:193–196.
  • CRETICOS PS, LICHTENSTEIN LM: Progress in the development of new methods of immunotherapy: potential application of immunostimulatory DNA-conjugated to allergens for treatment of allergic respiratory conditions. Arb. Paul Ehrlich Inst. Bundesamt Sera Impfitoffi Frankf A M(2003):304–312.

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