1,186
Views
57
CrossRef citations to date
0
Altmetric
Reviews

Toll-like receptor agonists: a patent review (2011 – 2013)

, , &

Bibliography

  • Medzhitov R. Recognition of microorganisms and activation of the immune response. Nature 2007;449:819-26
  • Iwasaki A, Medzhitov R. Regulation of adaptive immunity by the innate immune system. Science 2010;327:291-5
  • Akira S, Uematsu S, Takeuchi O. Pathogen recognition and innate immunity. Cell 2006;124:783-801
  • Moresco EMY, LaVine D, Beutler B. Toll-like receptors. Curr Biol 2011;21:R488-R93
  • Takeuchi O, Akira S. Pattern recognition receptors and inflammation. Cell 2010;140:805-20
  • Underhill DM, Ozinsky A. Toll-like receptors: key mediators of microbe detection. Curr Opin Immunol 2002;14:103-10
  • Medzhitov R, Preston-Hurlburt P, Janeway CA Jr. A human homolog of the Drosophila Toll protein signals activation of adaptive immunity. Nature 1997;388:394-6
  • Poltorak A, Smirnova I, He X, et al. Genetic and physical mapping of the Lps locus: identification of the Toll-4 receptor as a candidate gene in the critical region. Blood Cells Mol Dis 1998;24:340-55
  • Kawai T, Akira S. Toll-like receptors and their crosstalk with other innate receptors in infection and immunity. Immunity 2011;34:637-50
  • Lee CC, Avalos AM, Ploegh HL. Accessory molecules for Toll-like receptors and their function. Nat Rev Immunol 2012;12:168-79
  • Kawai T, Akira S. The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors. Nat Immunol 2010;11:373-84
  • O'Neill LAJ, Fitzgerald KA, Bowie AG. The Toll-IL-1 receptor adaptor family grows to five members. Trends Immunol 2003;24:286-90
  • Marshak-Rothstein A. Toll-like receptors in systemic autoimmune disease. Nat Rev Immunol 2006;6:823-35
  • Medzhitov R, Janeway C Jr. The Toll receptor family and microbial recognition. Trends Microbiol 2000;8:452-6
  • Kaisho T, Akira S. Regulation of dendritic cell function through toll-like receptors. Curr Mol Med 2003;3:759-71
  • Kopp E, Medzhitov R. Recognition of microbial infection by Toll-like receptors. Curr Opin Immunol 2003;15:396-401
  • Beutler B, Hoebe K, Du X, Ulevitch RJ. How we detect microbes and respond to them: the Toll-like receptors and their transducers. J Leukocyte Biol 2003;74:479-85
  • Pluddemann A, Mukhopadhyay S, Gordon S. Innate immunity to intracellular pathogens: macrophage receptors and responses to microbial entry. Immunol Rev 2011;240:11-24
  • Basith S, Manavalan B, Lee G, et al. Toll-like receptor modulators: a patent review (2006 - 2010). Expert Opin Ther Pat 2011;21:927-44
  • Netea MG, Wijmenga C, O'Neill LAJ. Genetic variation in Toll-like receptors and disease susceptibility. Nat Immunol 2012;13:535-42
  • Buchanan MM, Hutchinson M, Watkins LR, Yin H. Toll-like receptor 4 in CNS pathologies. J Neurochem 2010;114:13-27
  • Connolly DJ, O'Neill LAJ. New developments in Toll-like receptor targeted therapeutics. Curr Opin Pharmacol 2012;12:510-18
  • Hennessy EJ, Parker AE, O'Neill LAJ. Targeting Toll-like receptors: emerging therapeutics? Nat Rev Drug Discov 2010;9:293-307
  • Ohto U, Fukase K, Miyake K, Shimizu T. Structural basis of species-specific endotoxin sensing by innate immune receptor TLR4/MD-2. Proc Natl Acad Sci USA 2012;109:7421-6. S21/1-S21/7
  • Berke IC, Li Y, Modis Y. Structural basis of innate immune recognition of viral RNA. Cell Microbiol 2013;15:386-94
  • Tanji H, Ohto U, Shibata T, et al. Structural reorganization of the Toll-Like receptor 8 dimer Induced by agonistic ligands. Science 2013;339:1426-9
  • Park BS, Song DH, Kim HM, et al. The structural basis of lipopolysaccharide recognition by the TLR4-MD-2 complex. Nature 2009;458:1191-5
  • Liu L, Botos I, Wang Y, et al. Structural basis of Toll-Like receptor 3 signaling with double-stranded RNA. Science 2008;320:379-81
  • Jin MS, Kim SE, Heo JY, et al. Crystal structure of the TLR1-TLR2 heterodimer induced by binding of a tri-acylated lipopeptide. Cell 2007;130:1071-82
  • O'Neill LAJ, Bowie AG. The family of five: TIR-domain-containing adaptors in Toll-like receptor signalling. Nat Rev Immunol 2007;7:353-64
  • 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;101:15416-21
  • 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;5:1061-8
  • Pandey S, Agrawal DK. Immunobiology of Toll-like receptors: emerging trends. Immunol Cell Biol 2006;84:333-41
  • Krishnan J, Lee G, Choi S. Drugs targeting Toll-like receptors. Arch Pharm Res 2009;32:1485-502
  • Wang X, Smith C, Yin H. Targeting Toll-like receptors with small molecule agents. Chem Soc Rev 2013;42:4859-66
  • Moyle PM, Toth I. Modern subunit vaccines: development, components, and research opportunities. ChemMedChem 2013;8:360-76
  • Liu TY, Hussein WM, Toth I, Skwarczynski M. Advances in peptide-based human papillomavirus therapeutic vaccines. Curr Top Med Chem 2012;12:1581-92
  • Giddam AK, Zaman M, Skwarczynski M, Toth I. Liposome-based delivery system for vaccine candidates: constructing an effective formulation. Nanomedicine 2012;7:1877-93
  • Romagne F. Current and future drugs targeting one class of innate immunity receptors: the Toll-like receptors. Drug Discov Today 2006;12:80-7
  • Skwarczynski M, Toth I. Peptide-based subunit nanovaccines. Curr Drug Deliv 2011;8:282-9
  • Querec T, Bennouna S, Alkan S, et al. Yellow fever vaccine YF-17D activates multiple dendritic cell subsets via TLR2, 7, 8, and 9 to stimulate polyvalent immunity. J Exp Med 2006;203:413-24
  • Richardson MA, Ramirez T, Russell NC, Moye LA. Coley toxins immunotherapy: a retrospective review. Altern Ther Health Med 1999;5:42-7
  • Zacharski LR, Sukhatme VP. Coley's toxin revisited: immunotherapy or plasminogen activator therapy of cancer? J Thromb Haemost 2005;3:424-7
  • Morton DL, Eilber FR, Holmes EC, et al. BCG immunotherapy of malignant melanoma: summary of a seven-year experience. Ann Surg 1974;180:635-43
  • Silverstein MJ, DeKernion J, Morton DL. Malignant melanoma metastatic to the bladder. Regression following intratumor injection of BCG vaccine. JAMA 1974;229:688
  • Saint F, Patard JJ, Maille P, et al. T helper 1/2 lymphocyte urinary cytokine profiles in responding and nonresponding patients after 1 and 2 courses of Bacillus Calmette-Guerin for superficial bladder cancer. J Urol 2001;166:2142-7
  • Liu TY, Hussein WM, Jia ZF, et al. Self-adjuvanting polymer-peptide conjugates as therapeutic vaccine candidates against cervical cancer. Biomacromolecules 2013;14:2798-806
  • Skwarczynski M, Zaman M, Urbani CN, et al. Polyacrylate dendrimer nanoparticles: a self-adjuvanting vaccine delivery system. Angew Chem Int Edit Engl 2010;49:5742-5
  • Zaman M, Skwarczynski M, Malcolm JM, et al. Self-adjuvanting polyacrylic nanoparticulate delivery system for group A streptococcus (GAS) vaccine. Nanomedicine 2011;7:168-73
  • Galluzzi L, Vacchelli E, Eggermont A, et al. Trial Watch Experimental Toll-like receptor agonists for cancer therapy. Oncoimmunology 2012;1:699-716
  • Rzhetsky A, Nei M. Statistical properties of the ordinary least-squares, generalized least-squares, and minimum-evolution methods of phylogenetic inference. J Mol Evol 1992;35:367-75
  • Huelsenbeck JP, Ronquist F. Mrbayes: bayesian inference of phylogenetic trees. Bioinformatics 2001;17:754-5
  • Roach JC, Glusman G, Rowen L, et al. The evolution of vertebrate Toll-like receptors. Proc Natl Acad Sci USA 2005;102:9577-82
  • Hughes AL, Piontkivska H. Functional diversification of the toll-like receptor gene family. Immunogenetics 2008;60:249-56
  • Underhill DM, Ozinsky A, Haijar AM, et al. The toll-like receptor 2 is recruited to macrophage phagosomes and discriminates between pathogens. Nature 1999;401:811-15
  • Tapping RI. Innate immune sensing and activation of cell surface Toll-like receptors. Semin Immunol 2009;21:175-84
  • Miyake K. Innate immune sensing of pathogens and danger signals by cell surface Toll-like receptors. Semin Immunol 2007;19:3-10
  • Abdel-Aal ABM, El-Naggar D, Zaman M, et al. Design of fully synthetic, Self-adjuvanting vaccine incorporating the tumor-associated carbohydrate Tn antigen and lipoamino acid-based Toll-like receptor 2 ligand. J Med Chem 2012;55:6968-74
  • Abdel-Aal ABM, Al-Isae K, Zaman M, Toth I. Simple synthetic Toll-like receptor 2 ligands. Bioorg Med Chem Lett 2011;21:5863-5
  • Skwarczynski M, Dougall AM, Khoshnejad M, et al. Peptide-based subunit vaccine against hookworm infection. PLoS ONE 2012;7:e46870
  • Brightbill HD, Libraty DH, Krutzik SR, et al. Host defense mechanisms triggered by microbial lipoproteins through toll-like receptors. Science 1999;285:732-6
  • Aliprantis AO, Yang R-B, Mark MR, et al. Cell activation and apoptosis by bacterial lipoproteins through toll-like receptor-2. Science 1999;285:736-9
  • Zeng W-G, Eriksson E, Chua B, et al. Structural requirement for the agonist activity of the TLR2 ligand Pam2Cys. Amino Acids 2010;39:471-80
  • Eriksson EMY, Jackson DC. Recent advances with TLR2-targeting lipopeptide-based vaccines. Curr Protein Pept Sci 2007;8:412-17
  • Moyle PM, Toth I. Self-adjuvanting lipopeptide vaccines. Curr Med Chem 2008;15:506-16
  • Gallorini S, Berti F, Mancuso G, et al. Toll-like receptor 2 dependent immunogenicity of glycoconjugate vaccines containing chemically derived zwitterionic polysaccharides. Proc Natl Acad Sci USA 2009;106:17481-6. S81/1-S81/9
  • Liang S, Hosur KB, Nawar HF, et al. In vivo and in vitro adjuvant activities of the B subunit of Type IIb heat-labile enterotoxin (LT-IIb-B5) from Escherichia coli. Vaccine 2009;27:4302-8
  • Liu X, Wetzler LM, Massari P. The PorB porin from commensal Neisseria lactamica induces Th1 and Th2 immune responses to ovalbumin in mice and is a potential immune adjuvant. Vaccine 2008;26:786-96
  • Skwarczynski M, Toth I. Bioconjugation protocols: strategies and methods. 2nd edition. Science+Business Media: New York, LLC, 2011
  • Skwarczynski M, Zaman M, Toth I. Lipo-peptides/saccharides for peptide vaccine delivery. Elsevier Inc.: Burlington, Massachusetts, 2013. p. 571-9
  • Zhong W, Skwarczynski M, Toth I. Lipid core peptide system for gene,drug, and vaccine delivery. Aust J Chem 2009;62:956-67
  • Zaman M, Abdel-Aal AM, Phillipps KSM, et al. Structure-activity relationship of lipopeptide Group A streptococcus (GAS) vaccine candidates on toll-like receptor 2. Vaccine 2010;28:2243-8
  • Zaman M, Skwarczynski M, Toth I. Toll-like receptor 2 mediated dendritic cell activation-key target for lipopeptide vaccines design. Nova Science Publishers Inc.: New York, 2010
  • LIANG S. (LIAN-Individual) ACAD Sinica (SNIC). TLR-2 agonists and use thereof for stimulating immune responses. TW201311718; 2012
  • Muzio M, Bosisio D, Polentarutti N, et al. Differential expression and regulation of Toll-like receptors (TLR) in human leukocytes: selective expression of TLR3 in dendritic cells. J Immunol 2000;164:5998-6004
  • Zarember KA, Godowski PJ. Tissue expression of human toll-like receptors and differential regulation of toll-like receptor mRNAs in leukocytes in response to microbes, their products, and cytokines. J Immunol 2002;168:554-61
  • Sugiyama T, Hoshino K, Saito M, et al. Immunoadjuvant effects of polyadenylic:polyuridylic acids through TLR3 and TLR7. Int Immunol 2008;20:1-9
  • Salaun B, Coste I, Rissoan M-C, et al. TLR3 can directly trigger apoptosis in human cancer cells. J Immunol 2006;176:4894-901
  • Imperial Innovations Ltd, UK. Agonists of toll like receptor for treating cardiovascular disease and obesity. WO090005; 2012
  • Universita degli Studi di Roma “La Sapienza”, Italy. Combination of hypoxia-inducible factor-1 inhibitors and toll-like receptor-3 agonists for treating solid tumors. WO128436; 2011
  • Strayer DR, Carter WA, Stouch BC, et al. A double-blind, placebo-controlled, randomized, clinical trial of the TLR-3 agonist rintatolimod in severe cases of chronic fatigue syndrome. PLoS ONE 2012;7:e31334
  • Poltorak A, He X, Smirnova I, et al. Defective LPS signaling in C3H/HeJ and C57BL/10ScCr mice: mutations in Tlr4 gene. Science 1998;282:2085-8
  • Poltorak A, Ricciardi-Castagnoli P, Citterio S, Beutler B. Physical contact between lipopolysaccharide and Toll-like receptor 4 revealed by genetic complementation. Proc Natl Acad Sci USA 2000;97:2163-7
  • Ulevitch RJ. Endotoxin opens the tollgates to innate immunity. Nat Med 1999;5:144-5
  • Baldridge JR, McGowan P, Evans JT, et al. Taking a Toll on human disease: toll-like receptor 4 agonists as vaccine adjuvants and monotherapeutic agents. Expert Opin Biol Ther 2004;4:1129-38
  • Myers KR, Truchot AT. The endotoxic activity of Salmonella-minnesota R-595 lipid A depends on both the number and position of fatty-acid substitutions. Faseb J 1988;2:A911-A11
  • Ribi E, Parker R, Strain SM, et al. Peptides as requirement for immunotherapy of the guinea-pig line-10 tumor with endotoxins. Cancer Immunol Immunother 1979;7:43-58
  • Ulrich JT, Myers KR. Monophosphoryl lipid A as an adjuvant: past experiences and new directions. Pharm Biotechnol 1995;6:495-524
  • AV Therapeutics, Inc., USA. Synthetic Toll-like receptor-4 (TLR-4) agonist peptides. WO120073; 2013
  • Shanmugam A, Rajoria S, George AL, et al. Synthetic toll like receptor-4 (TLR-4) agonist peptides as a novel class of adjuvants. PLoS ONE 2012;7:e30839
  • Yeda Research and Development Co., Ltd., Israel. Toll-like receptor 4 agonist peptides with antigen composition for modulating TLR-4 mediated immune response and treating infectious disease or cancer. WO054329; 2013
  • GlaxoSmithKline Biologicals S.A., Belg. Toll-like receptor (TLR) agonist in combination with an antibody specific for an antigen. WO020724; 2013
  • Pfaar O, Barth C, Jaschke C, et al. Sublingual allergen-specific immunotherapy adjuvanted with monophosphoryl lipid A: a phase I/IIa study. Int Arch Allergy Immunol 2011;154:336-44
  • Andersen-Nissen E, Smith KD, Bonneau R, et al. A conserved surface on Toll-like receptor 5 recognizes bacterial flagellin. J Exp Med 2007;204:393-403
  • Hayashi F, Smith KD, Ozinsky A, et al. The innate immune response to bacterial flagellin is mediated by toll-like receptor 5. Nature 2001;410:1099-103
  • GlaxoSmithKline Biologicals S.A., Belg. TLR-5 receptor agonist as adjuvant for use in cutaneous immunization. WO072518; 2013
  • University of California. Uses of phospholipid conjugates of synthetic TLR7 agonists. US2013202629; 2011
  • University of California. Uses of phospholipid conjugates of synthetic TLR7 agonists. WO139348; 2011
  • Hayashi T, Chan M, Norton JT, et al. Additive melanoma suppression with intralesional phospholipid-conjugated TLR7 agonists and systemic IL-2. Melanoma Res 2011;21:66-75
  • VentiRx Pharmaceuticals, Inc., USA. Therapeutic use of a Toll-like receptor (TLR) agonist and combination therapy. WO045090; 2012
  • VentiRx Pharmaceuticals, Inc., USA. Toll-like receptor agonist formulations and their use. US018042l; 2013
  • Intermune, Inc. and Phillips R. Pirfenidone/Toll-like receptor (TLR) agonist compounds and methods of treating neutropenia. US218169; 2011
  • University of Southern California, USA. Methods and compositions of Toll-like receptor (TLR) agonists. US077263; 2011
  • Hemmi H, Kaisho T, Takeuchi O, et al. Small anti-viral compounds activate immune cells via the TLR7 MyD88-dependent signaling pathway. Nat Immunol 2002;3:196-200
  • Schoen MP, Schoen M. TLR7 and TLR8 as targets in cancer therapy. Oncogene 2008;27:190-9
  • Wang RF, Miyahara Y, Wang HY. Toll-like receptors and immune regulation: implications for cancer therapy. Oncogene 2008;27:181-9
  • Adams S, Kozhaya L, Martiniuk F, et al. Topical TLR7 agonist imiquimod can induce immune-mediated rejection of skin metastases in patients with breast cancer. Clin Cancer Res 2012;18:6748-57
  • Falke J, Lammers RJM, Arentsen HC, et al. Results of a phase 1 dose escalation study of intravesical TMX-101 in patients with nonmuscle invasive bladder cancer. J Urol 2013;189:2077-82
  • Birmachu W, Gleason RM, Bulbulian BJ, et al. Transcriptional networks in plasmacytoid dendritic cells stimulated with synthetic TLR 7 agonists. BMC Immunol 2007;8:26
  • Inglefield JR, Dumitru CD, Alkan SS, et al. TLR7 agonist 852A inhibition of tumor cell proliferation Is dependent on plasmacytoid dendritic cells and type I IFN. J Interferon Cytokine Res 2008;28:253-63
  • Weigel BJ, Cooley S, DeFor T, et al. Prolonged subcutaneous administration of 852A, a novel systemic toll-like receptor 7 agonist, to activate innate immune responses in patients with advanced hematologic malignancies. Am J Hematol 2012;87:953-6
  • Greiff L, Cervin A, Ahlstrom-Emanuelsson C, et al. Repeated intranasal TLR7 stimulation reduces allergen responsiveness in allergic rhinitis. Respir Res 2012;13:53
  • Bergmann JF, de BJ, Hotho DM, et al. Randomised clinical trial: anti-viral activity of ANA773, an oral inducer of endogenous interferons acting via TLR7, in chronic HCV. Aliment Pharmacol Ther 2011;34:443-53
  • Fidock MD, Souberbielle BE, Laxton C, et al. The innate immune response, clinical outcomes, and ex vivo HCV antiviral efficacy of a TLR7 agonist (PF-4878691). Clin Pharmacol Ther 2011;89:821-9
  • Heil F, Hemmi H, Hochrein H, et al. Species-specific recognition of single-stranded RNA via Toll-like receptor 7 and 8. Science 2004;303:1526-9
  • Jurk M, Heil F, Vollmer J, et al. Human TLR7 or TLR8 independently confer responsiveness to the antiviral compound R-848. Nat Immunol 2002;3:499
  • Campbell GR, Spector SA. Toll-like receptor 8 ligands activate a vitamin D mediated autophagic response that inhibits human immunodeficiency virus type 1. PLoS Pathog 2012;8:e1003017
  • Iwasaki A, Medzhitov R. Toll-like receptor control of the adaptive immune responses. Nat Immunol 2004;5:987-95
  • Jahrsdorfer B, Muehlenhoff L, Blackwell SE, et al. B-cell lymphomas differ in their responsiveness to CpG oligodeoxynucleotides. Clin Cancer Res 2005;11:1490-9
  • Krieg AM. Development of TLR9 agonists for cancer therapy. J Clin Invest 2007;117:1184-94
  • Spaner DE, Masellis A. Toll-like receptor agonists in the treatment of chronic lymphocytic leukemia. Leukemia 2007;21:53-60
  • Droemann D, Albrecht D, Gerdes J, et al. Human lung cancer cells express functionally active Toll-like receptor 9. Respir Res 2005;6:1
  • Li J, Ma Z, Tang Z-L, et al. CpG DNA-mediated immune response in pulmonary endothelial cells. Am J Physiol Lung Cell Mol Physiol 2004;287:L552-8
  • Platz J, Beisswenger C, Dalpke A, et al. Microbial DNA induces a host defense reaction of human respiratoryepithelial cells. J Immunol 2004;173:1219-23
  • Lebre MC, van dAAMG, van BL, et al. Human keratinocytes express functional Toll-like receptor 3, 4, 5, and 9. J Invest Dermatol 2007;127:331-41
  • Lee J, Mo J-H, Katakura K, et al. Maintenance of colonic homeostasis by distinctive apical TLR9 signalling in intestinal epithelial cells. Nat Cell Biol 2006;8:1327-36
  • Pedersen G, Andresen L, Matthiessen MW, et al. Expression of Toll-like receptor 9 and response to bacterial CpG oligodeoxynucleotides in human intestinal epithelium. Clin Exp Immunol 2005;141:298-306
  • Krieg AM. Antitumor applications of stimulating toll-like receptor 9 with CpG oligodeoxynucleotides. Curr Oncol Rep 2004;6:88-95
  • Vollmer J, Krieg AM. Immunotherapeutic applications of CpG oligodeoxynucleotide TLR9 agonists. Adv Drug Deliv Rev 2009;61:195-204
  • Hemmi H, Takeuchi O, Kawai T, et al. A Toll-like receptor recognizes bacterial DNA. Nature 2000;408:740-5
  • Yissum Research Development Co. of the Hebrew University of Jerusalem Ltd., Israel. Toll-like receptor 9 agonists for the treatment of anxiety-related disorders and inflammatory disorders. US136897; 2011
  • Idera Pharmaceuticals, Inc. Novel synthetic oligonucleotide-based agonists of TLR9 to modulate the immune response. WO2010088395; 2011
  • Zent CS, Smith BJ, Ballas ZK, et al. Phase I clinical trial of CpG oligonucleotide 7909 (PF-03512676) in patients with previously treated chronic lymphocytic leukemia. Leuk Lymphoma 2012;53:211-17
  • Rynkiewicz D, Rathkopf M, Sim I, et al. Marked enhancement of the immune response to BioThrax® (Anthrax Vaccine Adsorbed) by the TLR9 agonist CPG 7909 in healthy volunteers. Vaccine 2011;29:6313-20
  • Offersen R, Melchjorsen J, Paludan SR, et al. TLR9-adjuvanted pneumococcal conjugate vaccine induces antibody-independent memory responses in HIV-infected adults. Hum Vaccin Immunother 2012;8:1042-7
  • Tarhini AA, Leng S, Moschos SJ, et al. Safety and immunogenicity of vaccination with MART-1 (26-35, 27L), gp100 (209-217, 210M), and tyrosinase (368-376, 370D) in adjuvant with PF-3512676 and GM-CSF in metastatic melanoma. J Immunother 2012;35:359-66
  • Krieg AM. Toll-like receptor 9 (TLR9) agonists in the treatment of cancer. Oncogene 2008;27:161-7
  • Azzoli CG, Baker S Jr, Temin S, et al. American society of clinical oncology clinical practice guideline update on chemotherapy for stage IV non-small-cell lung cancer. J Clin Oncol 2009;27:6251-66
  • Hirsh V, Paz-Ares L, Boyer M, et al. Randomized phase III trial of paclitaxel/carboplatin with or without PF-3512676 (Toll-like receptor 9 agonist) as first-line treatment for advanced non-small-cell lung cancer. J Clin Oncol 2011;29:2667-74
  • Manegold C, van ZN, Szczesna A, et al. A phase III randomized study of gemcitabine and cisplatin with or without PF-3512676 (TLR9 agonist) as first-line treatment of advanced non-small-cell lung cancer. Ann Oncol 2012;23:72-7
  • Millward M, Underhill C, Lobb S, et al. Phase I study of tremelimumab (CP-675 206) plus PF-3512676 (CPG 7909) in patients with melanoma or advanced solid tumours. Br J Cancer 2013;108:1998-2004
  • Cohn L, Elias JA, Chupp GL. Asthma: mechanisms of disease persistence and progression. Annu Rev Immunol 2004;22:789-815
  • Kuramoto E, Yano O, Kimura Y, et al. Oligonucleotide sequences required for natural killer cell activation. Jpn J Cancer Res 1992;83:1128-31
  • Speiser DE, Schwarz K, Baumgaertner P, et al. Memory and effector CD8 T-cell responses after nanoparticle vaccination of melanoma patients. J Immunother 2010;33:848-58
  • Huber JP, Ramos HJ, Gill MA, Farrar JD. Cutting edge: type I IFN reverses human Th2 commitment and stability by suppressing GATA3. J Immunol 2010;185:813-17
  • Ito T, Yang M, Wang Y-H, et al. Plasmacytoid dendritic cells prime IL-10-producing T regulatory cells by inducible costimulator ligand. J Exp Med 2007;204:105-15
  • Krieg AM. Therapeutic potential of Toll-like receptor 9 activation. Nat Rev Drug Discov 2006;5:471-84
  • Bachmann MF, Jennings GT. Vaccine delivery: a matter of size, geometry, kinetics and molecular patterns. Nat Rev Immunol 2010;10:787-96
  • Beeh K-M, Kanniess F, Wagner F, et al. The novel TLR-9 agonist QbG10 shows clinical efficacy in persistent allergic asthma. J Allergy Clin Immunol 2013;131:866-74
  • Klimek L, Willers J, Hammann-Haenni A, et al. Assessment of clinical efficacy of CYT003-QbG10 in patients with allergic rhinoconjunctivitis: a phase IIb study. Clin Exp Allergy 2011;41:1305-12
  • Sablan BP, Kim DJ, Barzaga NG, et al. Demonstration of safety and enhanced seroprotection against hepatitis B with investigational HBsAg-1018 ISS vaccine compared to a licensed hepatitis B vaccine. Vaccine 2012;30:2689-96
  • Creed TJ, Lee RW, Newcomb PV, et al. The effects of cytokines on suppression of lymphocyte proliferation by dexamethasone. J Immunol 2009;183:164-71
  • Musch E, Lutfi T, von SP, et al. Topical treatment with the Toll-like receptor agonist DIMS0150 has potential for lasting relief of symptoms in patients with chronic active ulcerative colitis by restoring glucocorticoid sensitivity. Inflamm Bowel Dis 2013;19:283-92
  • The University of California. TLR agonists. US165455; 2013
  • Wu CCN, Hayashi T, Takabayashi K, et al. Immunotherapeutic activity of a conjugate of a Toll-like receptor 7 ligand. Proc Natl Acad Sci USA 2007;104:3990-5
  • President and Fellows of Harvard College, USA; Dana-Farber Cancer Institute, Inc. Controlled delivery of TLR agonists in structural polymeric devices. US202707; 2013
  • President and Fellows of Harvard College, USA; Dana-Farber Cancer Institute, Inc. Controlled delivery of TLR agonists in structural polymeric devices. WO106852; 2013
  • GlaxoSmithKline Biologicals S.A., Belg. Oral vaccine comprising an antigen and a toll-like receptor agonist. WO151431; 2011
  • Ahonen CL, Doxsee CL, McGurran SM, et al. Combined TLR and CD40 triggering induces potent CD8+ T cell expansion with variable dependence on type I IFN. J Exp Med 2004;199:775-84
  • Delucia D. Adjuvant combinations comprising a microbial TLR agonist, a CD40 or 4-1BB agonist, and optionally an antigen and the use thereof for inducing a synergistic enhancement in cellular immunity. US045414; 2012
  • Chu Nantes - Univ Nantes. TLR 4 and 9 receptors agonists for preventing septic complications of post-traumatic immunodepression in patients hospitalized for severe traumatic injuries. US028936; 2013
  • Immurx, Inc., USA. Use of TLR agonists and/or type 1 interferons to alleviate toxicity of TNF-R agonist therapeutic regimens. US182847; 2011
  • Ludwig Institute for Cancer Research, USA. Use of iNKT or TLR agonists for protecting against or treating a disease such as acute infection or cancer. US293658; 2011
  • The Provost, Fellows and Scholars of the College of the College of the Holy and Undivided Triniy of Queen Elizabeth near London. Ire compositions comprising a Toll-like receptor (TLR) agonist and an immune modulator for treating Th1-mediated conditions, such as cancer and infectious diseases. NZ569086; 2011
  • Infectious Disease Research Institute, USA. Vaccine composition containing synthetic adjuvant. US8273361B2; 2008
  • Alfthan H, Haglund C, Roberts P, Stenman UH. Elevation of free beta subunit of human choriogonadotropin and core beta fragment of human choriogonadotropin in the serum and urine of patients with malignant pancreatic and biliary disease. Cancer Res 1992;52:4628-33
  • Hotakainen K, Liungberg B, Paju A, et al. The free beta-subunit of human chorionic gonadotropin as a prognostic factor in renal cell carcinoma. Br J Cancer 2002;86:185-9
  • Lundin M, Nordling S, Lundin J, et al. Tissue expression of human chorionic gonadotropin beta predicts outcome in colorectal cancer: a comparison with serum expression. Int J Cancer 2001;95:18-22
  • Syrigos KN, Fyssas I, Konstandoulakis MM, et al. Beta human chorionic gonadotropin concentrations in serum of patients with pancreatic adenocarcinoma. Gut 1998;42:88-91
  • Triozzi PL, Stevens VC. Human chorionic gonadotropin as a target for cancer vaccines. Oncol Rep 1999;6:7-17
  • Morse MA, Chapman R, Powderly J, et al. Phase I study utilizing a novel antigen-presenting cell-targeted vaccine with Toll-like receptor stimulation to induce immunity to self-antigens in cancer patients. Clin Cancer Res 2011;17:4844-53
  • ClinicalTrials. Available from: http://www.clinicaltrials.gov/

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.