The novel TLR-9 agonist QbG10 shows clinical efficacy in persistent allergic asthma

Journal of Allergy and Clinical Immunology

Volumn 131, Issue 3, 2013, Pages 866-874

  Beeh, Kai Michael ^a   Kanniess, Frank ^b   Wagner, Frank ^c   Schilder, Cordula ^d   Naudts, Ingomar ^b   Hammann Haenni, Anya ^e   Willers, Joerg ^e   Stocker, Hans ^e   Mueller, Philipp ^e   Bachmann, Martin F ^e   Renner, Wolfgang A ^e  

^a Institut fur Atemwegsforschung INSAF   (Germany)

^b KLB Healthresearch Lübeck ^*  (Germany)

^c CHARITÉ UNIVERSITÄTSMEDIZIN BERLIN   (Germany)

^d Health Center Schilder   (Germany)

^e CYTOS BIOTECHNOLOGY AG   (Switzerland)

Author keywords

clinical trial; immune modulator; Persistent allergic asthma; Toll like receptor 9; virus like particle

Indexed keywords

ANTIASTHMATIC AGENT; BECLOMETASONE DIPROPIONATE; NITRIC OXIDE; PLACEBO; QBG10; SALBUTAMOL; TOLL LIKE RECEPTOR 9; TOLL LIKE RECEPTOR AGONIST; UNCLASSIFIED DRUG;

ADULT; ALLERGIC ASTHMA; ARTICLE; CONTROLLED STUDY; DOUBLE BLIND PROCEDURE; DRUG EFFICACY; DRUG SAFETY; DRUG TOLERABILITY; DRUG WITHDRAWAL; DYSPNEA; EOSINOPHIL; FEMALE; FORCED EXPIRATORY VOLUME; HEADACHE; HUMAN; IMMUNE SYSTEM; INJECTION SITE EDEMA; INJECTION SITE ERYTHEMA; INJECTION SITE INDURATION; INJECTION SITE PAIN; INJECTION SITE PRURITUS; INJECTION SITE REACTION; INJECTION SITE SWELLING; MAJOR CLINICAL STUDY; MALE; OROPHARYNX PAIN; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; RHINITIS; RHINOPHARYNGITIS; RHINORRHEA; TREATMENT OUTCOME; VIRUS LIKE AGENT;

ADOLESCENT; ADULT; AGED; ANTI-ASTHMATIC AGENTS; ASTHMA; BECLOMETHASONE; DOUBLE-BLIND METHOD; FEMALE; FORCED EXPIRATORY VOLUME; GLUCOCORTICOIDS; HUMANS; IMMUNOGLOBULIN E; MALE; MIDDLE AGED; NITRIC OXIDE; OLIGONUCLEOTIDES; TOLL-LIKE RECEPTOR 9; YOUNG ADULT;

EID: 84875219804     PISSN: 00916749     EISSN: 10976825     Source Type: Journal    
DOI: 10.1016/j.jaci.2012.12.1561     Document Type: Article

References (44)

1. F. Onyirimba, A. Apter, S. Reisine, M. Litt, C. McCusker, and M. Connors Direct clinician-to-patient feedback discussion of inhaled steroid use: its effect on adherence Ann Allergy Asthma Immunol 90 2003 411 415
2. B. Bender, H. Milgrom, and C. Rand Nonadherence in asthmatic patients: is there a solution to the problem? Ann Allergy Asthma Immunol 79 1997 177 185 quiz 85-6
3. A.E. Tattersfield, T.W. Harrison, R.B. Hubbard, and K. Mortimer Safety of inhaled corticosteroids Proc Am Thorac Soc 1 2004 171 175
4. L. Cohn, J.A. Elias, and G.L. Chupp Asthma: mechanisms of disease persistence and progression Annu Rev Immunol 22 2004 789 815
5. P.S. Creticos, J.T. Schroeder, R.G. Hamilton, S.L. Balcer-Whaley, A.P. Khattignavong, and R. Lindblad Immunotherapy with a ragweed-Toll-like receptor 9 agonist vaccine for allergic rhinitis N Engl J Med 355 2006 1445 1455
6. S.M. Walker, V.A. Varney, M. Gaga, M.R. Jacobson, and S.R. Durham Grass pollen immunotherapy: efficacy and safety during a 4-year follow-up study Allergy 50 1995 405 413
7. T.B. Casale, and J.R. Stokes Future forms of immunotherapy J Allergy Clin Immunol 127 2011 8 15
8. D.E. Speiser, K. Schwarz, P. Baumgaertner, V. Manolova, E. Devevre, and W. Sterry Memory and effector CD8 T-cell responses after nano-particle vaccination of melanoma patients J Immunother 33 2010 848 858
9. E. Kuramoto, O. Yano, Y. Kimura, M. Baba, T. Makino, and S. Yamamoto Oligonucleotide sequences required for natural killer cell activation Jpn J Cancer Res 83 1992 1128 1131
10. C.L. Cooper, H.L. Davis, M.L. Morris, S.M. Efler, A.M. Krieg, and Y. Li Safety and immunogenicity of CPG 7909 injection as an adjuvant to Fluarix influenza vaccine Vaccine 22 2004 3136 3143
11. J.W. Friedberg, H. Kim, M. McCauley, E.M. Hessel, P. Sims, and D.C. Fisher Combination immunotherapy with a CpG oligonucleotide (1018 ISS) and rituximab in patients with non-Hodgkin lymphoma: increased interferon-alpha/ beta-inducible gene expression, without significant toxicity Blood 105 2005 489 495
12. S.A. Halperin, G. Van Nest, B. Smith, S. Abtahi, H. Whiley, and J.J. Eiden A phase I study of the safety and immunogenicity of recombinant hepatitis B surface antigen co-administered with an immunostimulatory phosphorothioate oligonucleotide adjuvant Vaccine 21 2003 2461 2467
13. D.E. Speiser, D. Lienard, N. Rufer, V. Rubio-Godoy, D. Rimoldi, and F. Lejeune Rapid and strong human CD8+ T cell responses to vaccination with peptide, IFA, and CpG oligodeoxynucleotide 7909 J Clin Invest 115 2005 739 746
14. A. Carpentier, F. Laigle-Donadey, S. Zohar, L. Capelle, A. Behin, and A. Tibi Phase 1 trial of a CpG oligodeoxynucleotide for patients with recurrent glioblastoma Neuro Oncol 8 2006 60 66
15. M.A. Hofmann, C. Kors, H. Audring, P. Walden, W. Sterry, and U. Trefzer Phase 1 evaluation of intralesionally injected TLR9-agonist PF-3512676 in patients with basal cell carcinoma or metastatic melanoma J Immunother 31 2008 520 527
16. A.M. Krieg Therapeutic potential of Toll-like receptor 9 activation Nat Rev Drug Discov 5 2006 471 484
17. M.F. Bachmann, and G.T. Jennings Vaccine delivery: a matter of size, geometry, kinetics and molecular patterns Nat Rev Immunol 10 2010 787 796
18. J.P. Huber, H.J. Ramos, M.A. Gill, and J.D. Farrar Cutting edge: type I IFN reverses human Th2 commitment and stability by suppressing GATA3 J Immunol 185 2010 813 817
19. T. Ito, M. Yang, Y.H. Wang, R. Lande, J. Gregorio, and O.A. Perng Plasmacytoid dendritic cells prime IL-10-producing T regulatory cells by inducible costimulator ligand J Exp Med 204 2007 105 115
20. G. Senti, P. Johansen, S. Haug, C. Bull, C. Gottschaller, and P. Muller Use of A-type CpG oligodeoxynucleotides as an adjuvant in allergen-specific immunotherapy in humans: a phase I/IIa clinical trial Clin Exp Allergy 39 2009 562 570
21. L. Klimek, J. Willers, A. Hammann-Haenni, O. Pfaar, H. Stocker, and P. Mueller Assessment of clinical efficacy of CYT003-QbG10 in patients with allergic rhinoconjunctivitis: a phase IIb study Clin Exp Allergy 41 2011 1305 1312
22. F. Kanniess, K. Richter, S. Janicki, M.B. Schleiss, R.A. Jorres, and H. Magnussen Dose reduction of inhaled corticosteroids under concomitant medication with montelukast in patients with asthma Eur Respir J 20 2002 1080 1087
23. E.F. Juniper, J. Bousquet, L. Abetz, and E.D. Bateman Identifying 'well-controlled' and 'not well-controlled' asthma using the Asthma Control Questionnaire Respir Med 100 2006 616 621
24. J. Belda, K. Parameswaran, C. Lemiere, D. Kamada, P.M. O'Byrne, and F.E. Hargreave Predictors of loss of asthma control induced by corticosteroid withdrawal Can Respir J 13 2006 129 133
25. E.F. Juniper, K. Svensson, A.C. Mork, and E. Stahl Measurement properties and interpretation of three shortened versions of the asthma control questionnaire Respir Med 99 2005 553 558
26. P.J. Barnes Cytokine modulators as novel therapies for airway disease Eur Respir J Suppl 34 2001 67s-77
27. M. Humbert, R. Beasley, J. Ayres, R. Slavin, J. Hebert, and J. Bousquet Benefits of omalizumab as add-on therapy in patients with severe persistent asthma who are inadequately controlled despite best available therapy (GINA 2002 step 4 treatment): INNOVATE Allergy 60 2005 309 316
28. P. Haldar, C.E. Brightling, B. Hargadon, S. Gupta, W. Monteiro, and A. Sousa Mepolizumab and exacerbations of refractory eosinophilic asthma N Engl J Med 360 2009 973 984
29. J. Corren, W. Busse, E.O. Meltzer, L. Mansfield, G. Bensch, and J. Fahrenholz A randomized, controlled, phase 2 study of AMG 317, an IL-4R alpha antagonist, in patients with asthma Am J Respir Crit Care Med 181 2010 788 796
30. J.M. Parker, C.K. Oh, C. LaForce, S.D. Miller, D.S. Pearlman, and C. Le Safety profile and clinical activity of multiple subcutaneous doses of MEDI-528, a humanized anti-interleukin-9 monoclonal antibody, in two randomized phase 2a studies in subjects with asthma BMC Pulm Med 11 2011 14
31. S.A. Bryan, B.J. O'Connor, S. Matti, M.J. Leckie, V. Kanabar, and J. Khan Effects of recombinant human interleukin-12 on eosinophils, airway hyper-responsiveness, and the late asthmatic response Lancet 356 2000 2149 2153
32. H.U. Simon, H. Seelbach, R. Ehmann, and M. Schmitz Clinical and immunological effects of low-dose IFN-alpha treatment in patients with corticosteroid-resistant asthma Allergy 58 2003 1250 1255
33. L.C. Borish, H.S. Nelson, M.J. Lanz, L. Claussen, J.B. Whitmore, and J.M. Agosti Interleukin-4 receptor in moderate atopic asthma: a phase I/II randomized, placebo-controlled trial Am J Respir Crit Care Med 160 1999 1816 1823
34. L.C. Borish, H.S. Nelson, J. Corren, G. Bensch, W.W. Busse, and J.B. Whitmore Efficacy of soluble IL-4 receptor for the treatment of adults with asthma J Allergy Clin Immunol 107 2001 963 970
35. M. Soler, J. Matz, R. Townley, R. Buhl, J. O'Brien, and H. Fox The anti-IgE antibody omalizumab reduces exacerbations and steroid requirement in allergic asthmatics Eur Respir J 18 2001 254 261
36. E.D. Bateman, S.S. Hurd, P.J. Barnes, J. Bousquet, J.M. Drazen, and M. FitzGerald Global strategy for asthma management and prevention: GINA executive summary Eur Respir J 31 2008 143 178
37. L. Roussel, S. Robins, A. Schachter, J. Berube, Q. Hamid, and S. Rousseau Steroids and extracellular signal-regulated kinase 1/2 activity suppress activating transcription factor 3 expression in patients with severe asthma J Allergy Clin Immunol 127 2011 1632 1634
38. J.R. Tversky, T.V. Le, A.P. Bieneman, K.L. Chichester, R.G. Hamilton, and J.T. Schroeder Human blood dendritic cells from allergic subjects have impaired capacity to produce interferon-alpha via Toll-like receptor 9 Clin Exp Allergy 38 2008 781 788
39. V. Manolova, A. Flace, M. Bauer, K. Schwarz, P. Saudan, and M.F. Bachmann Nanoparticles target distinct dendritic cell populations according to their size Eur J Immunol 38 2008 1404 1413
40. E.A. Moseman, X. Liang, A.J. Dawson, A. Panoskaltsis-Mortari, A.M. Krieg, and Y.J. Liu Human plasmacytoid dendritic cells activated by CpG oligodeoxynucleotides induce the generation of CD4+CD25+ regulatory T cells J Immunol 173 2004 4433 4442
41. H.J. de Heer, H. Hammad, T. Soullie, D. Hijdra, N. Vos, and M.A. Willart Essential role of lung plasmacytoid dendritic cells in preventing asthmatic reactions to harmless inhaled antigen J Exp Med 200 2004 89 98
42. W.C. Moore, E.R. Bleecker, D. Curran-Everett, S.C. Erzurum, B.T. Ameredes, and L. Bacharier Characterization of the severe asthma phenotype by the National Heart, Lung, and Blood Institute's Severe Asthma Research Program J Allergy Clin Immunol 119 2007 405 413
43. M. Humbert, S.R. Durham, P. Kimmitt, N. Powell, B. Assoufi, and R. Pfister Elevated expression of messenger ribonucleic acid encoding IL-13 in the bronchial mucosa of atopic and nonatopic subjects with asthma J Allergy Clin Immunol 99 1997 657 665
44. S.J. Levine, and S.E. Wenzel Narrative review: the role of Th2 immune pathway modulation in the treatment of severe asthma and its phenotypes Ann Intern Med 152 2010 232 237