Immune modulation for treatment of allergic disease

Immunological Reviews

Volumn 242, Issue 1, 2011, Pages 258-271

  Nguyen, Tran Hoai T ^a   Casale, Thomas B ^a  

^a CREIGHTON UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Allergic rhinitis; Asthma; Cytokine; Immune modulator; Immunotherapy; Toll like receptor

Indexed keywords

ACT 129968; AIR 645; ALTRAKINCEPT; AMG 317; ANRUKINZUMAB; AVP 13358; ENOKIZUMAB; IMA 026; IMMUNOMODULATING AGENT; INTERLEUKIN 13; INTERLEUKIN 13 ANTIBODY; INTERLEUKIN 19; INTERLEUKIN 2; INTERLEUKIN 3 RECEPTOR; INTERLEUKIN 4; INTERLEUKIN 4 RECEPTOR; INTERLEUKIN 5; LEBRIKIZUMAB; LUMILIXIMAB; OC 000459; PASCOLIZUMAB; PIOGLITAZONE; PITRAKINRA; PLACEBO; QAX 576; R 0498991; ROSIGLITAZONE; TRALOKINUMAB; UNCLASSIFIED DRUG; UNINDEXED DRUG; VIDUPIPRANT;

ALLERGIC ASTHMA; ALLERGIC DISEASE; ALLERGIC RHINITIS; ARTICLE; ASTHMA; CARDIOVASCULAR DISEASE; CELLULAR IMMUNITY; CLINICAL TRIAL (TOPIC); CYTOKINE PRODUCTION; DRUG SAFETY; DRUG TOLERABILITY; EOSINOPHILIA; EOSINOPHILIC ESOPHAGITIS; HUMAN; IMMUNOMODULATION; NONHUMAN; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PHENOTYPE; PRIORITY JOURNAL; RESPIRATORY TRACT ALLERGY; TH1 CELL; TH2 CELL; TREATMENT OUTCOME; UNSPECIFIED SIDE EFFECT;

ADOLESCENT; ADULT; ANIMALS; ASTHMA; CHILD; CLINICAL TRIALS AS TOPIC; EOSINOPHILIC ESOPHAGITIS; HUMANS; HYPERSENSITIVITY; IMMUNITY; IMMUNOGLOBULIN E; IMMUNOLOGIC FACTORS; IMMUNOMODULATION; INFLAMMATION; INTERLEUKIN-13; INTERLEUKIN-4; MICE; RECEPTORS, INTERLEUKIN-13; RHINITIS, ALLERGIC, SEASONAL; TH1 CELLS; TH1-TH2 BALANCE; TH2 CELLS; TOLL-LIKE RECEPTORS;

EID: 79959355853     PISSN: 01052896     EISSN: 1600065X     Source Type: Journal    
DOI: 10.1111/j.1600-065X.2011.01034.x     Document Type: Article

References (110)

1. Borish LC, et al. Efficacy of soluble IL-4 receptor for the treatment of adults with asthma. J Allergy Clin Immunol 2001;107:963-970.
2. Bree A, et al. IL-13 blockade reduces lung inflammation after Ascaris suum challenge in cynomolgus monkeys. J Allergy Clin Immuno 2007;119:1251-1257.
3. Blanchard C, Mishra A, Saito-Akei H, Monk P, Anderson I, Rothenberg ME. Inhibition of human interleukin-13-induced respiratory and oesophageal inflammation by anti-human-interleukin-13 antibody (CAT-354). Clin Exp Allergy 2005;35:1096-1103.
4. Kariyawasam HH, et al. Effects of Anti-IL-13 (Novartis QAX576) on inflammatory responses following nasal allergen challenge (NAC). Am J Respir Crit Care Med 2009;179(A3642):???-???.
5. Clinicaltrials.gov. Efficacy of QAX576 in Asthma. 2010. Available from
6. Clinicaltrials.gov. Efficacy and Safety of QAX576 in Patients with Eosinophilic Esophagitis. 2010. Available from
7. Clinicaltrials.gov. Study Evaluating the Effect of IMA-026 on Allergen-Induced Late Asthma Response in Mild Asthma. 2009. Available from
8. Clinicaltrials.gov. Study Evaluating the Effect of IMA-638 in Subjects with Persistent Asthma. 2009. Available from
9. Clinicaltrials.gov. Study Evaluating the Effects of IMA-638 on Allergen-Induced Airway Responses in Subjects with Mild Atopic Asthma. 2008. Available from
10. Oh CK, et al. An open-label, single-dose bioavailability study of the pharmacokinetics of CAT-354 after subcutaneous and intravenous administration in healthy males. Br J Clin Pharmacol 2010;69:645-655.
11. Clinicaltrials.gov. Study to Evaluate the Safety and Efficacy of CAT-354. 2010. Available from
12. Clinicaltrials.gov. A Study of Lebrikizumab (MILR1444A) in Adult Patients with Asthma Who Are Inadequately Controlled on Inhaled Corticosteroids (MILLY). 2010. Available from
13. Corren J, et al. A randomized, controlled, phase 2 study of AMG 317, an IL-4Ralpha antagonist, in patients with asthma. Am J Respir Crit Care Med 2010;181:788-796.
14. Hodges MR, et al. Randomized, double-blind, placebo controlled first in human study of inhaled AIR645, an IL-4Ra oligonucleotide, in healthy volunteers. Am J Respir Crit Care Med 2009;A3640.
15. Clinicaltrials.gov. Study Evaluating the Effects of AIR 645 on Allergen-Induced Airway Responses in Subjects with Mild Atopic Asthma. 2010. Available from
16. Wenzel S, Wilbraham D, Fuller R, Getz EB, Longphre M. Effect of an interleukin-4 variant on late phase asthmatic response to allergen challenge in asthmatic patients: results of two phase 2a studies. Lancet 2007;370:1422-1431.
17. Aerovance. Aeroderm. 2010. Available from
18. Temann UA, Ray P, Flavell RA. Pulmonary overexpression of IL-9 induces Th2 cytokine expression, leading to immune pathology. J Clin Invest 2002;109:29-39.
19. Levitt RC, et al. IL-9 pathway in asthma: new therapeutic targets for allergic inflammatory disorders. J Allergy Clin Immunol 1999;103:S485-S491.
20. Clinicaltrials.gov. A Study to Evaluate the Effectiveness and Safety of MEDI-528 in Adults. 2010. Available from
21. Parker J, et al. Randomized, double-blind, placebo-controlled, multicenter Phase 2A study to evaluate the effect of a humanized interleukin-9 monoclonal antibody (MEDI-528) on exercise-induced bronchospasm. Am J Respir Crit Care Med 2010;181:A5394.
22. Tanaka A, et al. Suplatast tosilate, a potent anti-allergic agent, inhibits a remodeling in a mouse model of bronchial asthma. Am J Respir Crit Care Med 2010;181:A5678.
23. Shimizu S, Hattori R, Majima Y, Shimizu T. Th2 cytokine inhibitor suplatast tosilate inhibits antigen-induced mucus hypersecretion in the nasal epithelium of sensitized rats. Ann Otol Rhinol Laryngol 2009;118:67-72.
24. Shahriar M, et al. Suplatast tosilate inhibits histamine signaling by direct and indirect downregulation of histamine H1 receptor gene expression through suppression of histidine decarboxylase and IL-4 gene transcriptions. J Immunol 2009;183:2133-2141.
25. Tanaka A, et al. Inhibitory effects of suplatast tosilate on the differentiation and function of monocyte-derived dendritic cells from patients with asthma. Clin Exp Allergy 2007;37:1083-1089.
26. Washio Y, et al. Suplatast tosilate affects the initial increase in specific IgE and interleukin-4 during immunotherapy for perennial allergic rhinitis. Acta Otolaryngol Suppl 1998;538:126-132.
27. Tamaoki J, et al. Effect of suplatast tosilate, a Th2 cytokine inhibitor, on steroid-dependent asthma: a double-blind randomised study. Lancet 2000;356:273-278.
28. Wada M, Nagata S, Kudo T, Shimizu T, Yamashiro Y. Effect of suplatast tosilate on antileukotriene non-responders with mild-to-moderate persistent asthma. Allergol Int 2009;58:389-393.
29. Hoshino M, Fujita Y, Saji J, Inoue T, Nakagawa T, Miyazawa T. Effect of suplatast tosilate on goblet cell metaplasia in patients with asthma. Allergy 2005;60:1394-1400.
30. Sano Y, et al. Effects of suplatast tosilate on allergic eosinophilic airway inflammation in patients with mild asthma. J Allergy Clin Immunol 2003;111:958-966.
31. Yoshida M, et al. Effect of suplatast tosilate on airway hyperresponsiveness and inflammation in asthma patients. J Asthma 2002;39:545-552.
32. Miyachi Y, Katayama I, Furue M. Suplatast/tacrolimus combination therapy for refractory facial erythema in adult patients with atopic dermatitis: a meta-analysis study. Allergol Int 2007;56:269-275.
33. Murakami T, et al. Topical suplatast tosilate (IPD) ameliorates Th2 cytokine-mediated dermatitis in caspase-1 transgenic mice by downregulating interleukin-4 and interleukin-5. Br J Dermatol 2006;155:27-32.
34. Zhang DH, et al. Inhibition of allergic inflammation in a murine model of asthma by expression of a dominant-negative mutant of GATA-3. Immunity 1999;11:473-482.
35. Woerly G, et al. Peroxisome proliferator-activated receptors alpha and gamma down-regulate allergic inflammation and eosinophil activation. J Exp Med 2003;198:411-421.
36. Belvisi MG, Hele DJ. Peroxisome proliferator-activated receptors as novel targets in lung disease. Chest 2008;134:152-157.
37. Denning GM, Stoll LL. Peroxisome proliferator-activated receptors: potential therapeutic targets in lung disease? Pediatr Pulmonol 2006;41:23-34.
38. Spears M, et al. Bronchodilatory effect of the PPAR-gamma agonist rosiglitazone in smokers with asthma. Clin Pharmacol Ther 2009;86:49-53.
39. Sandhu MS, Dimov V, Romero T, Wichman T, Casale TB. Effects of rosiglitazone on airway hyperresponsiveness and obstruction in asthma. J Allergy Clin Immunol 2010;5:AB66.
40. Clinicaltrials.gov. Pilot Study of Pioglitazone for the Treatment of Moderate to Severe Asthma in Obese Asthmatics (GLITZ). 2010. Available from
41. Clinicaltrials.gov. A Randomized, Placebo-Controlled, Double-Blind Pilot Study of Pioglitazone Hydrochloride in Severe, Refractory Asthma. 2010. Available from
42. Wang YH, Liu YJ. OX40-OX40L interactions: a promising therapeutic target for allergic diseases? J Clin Invest 2007;117:3655-3657.
43. Hoshino A, et al. Critical role for OX40 ligand in the development of pathogenic Th2 cells in a murine model of asthma. Eur J Immunol 2003;33:861-869.
44. Clinicaltrials.gov. A Study of RO4989991 in Patients with Allergic Rhinitis. 2010. Available from
45. Clinicaltrials.gov. A Study of huMAb OX40L in the Prevention of Allergen-Induced Airway Obstruction in Adults with Mild Allergic Asthma. 2010. Available from
46. Lin H, et al. Omalizumab rapidly decreases nasal allergic response and FcepsilonRI on basophils. J Allergy Clin Immunol 2004;113:297-302.
47. Prussin C, Griffith DT, Boesel KM, Lin H, Foster B, Casale TB. Omalizumab treatment downregulates dendritic cell FcepsilonRI expression. J Allergy Clin Immunol 2003;112:1147-1154.
48. van Rensen EL, et al. Eosinophils in bronchial mucosa of asthmatics after allergen challenge: effect of anti-IgE treatment. Allergy 2009;64:72-80.
49. Busse W, et al. Omalizumab, anti-IgE recombinant humanized monoclonal antibody, for the treatment of severe allergic asthma. J Allergy Clin Immunol 2001;108:184-190.
50. Milgrom H, et al. Treatment of childhood asthma with anti-immunoglobulin E antibody (omalizumab). Pediatrics 2001;108:E36.
51. Soler M, et al. The anti-IgE antibody omalizumab reduces exacerbations and steroid requirement in allergic asthmatics. Eur Respir J 2001;18:254-261.
52. Corren J, Casale T, Deniz Y, Ashby M. Omalizumab, a recombinant humanized anti-IgE antibody, reduces asthma-related emergency room visits and hospitalizations in patients with allergic asthma. J Allergy Clin Immunol 2003;111:87-90.
53. Wu AC, Paltiel AD, Kuntz KM, Weiss ST, Fuhlbrigge AL. Cost-effectiveness of omalizumab in adults with severe asthma: results from the Asthma Policy Model. J Allergy Clin Immunol 2007;120:1146-1152.
54. Casale TB, et al. Effect of omalizumab on symptoms of seasonal allergic rhinitis: a randomized controlled trial. JAMA 2001;286:2956-2967.
55. Hanf G, Noga O, O'Connor A, Kunkel G. Omalizumab inhibits allergen challenge-induced nasal response. Eur Respir J 2004;23:414-418.
56. Chervinsky P, et al. Omalizumab, an anti-IgE antibody, in the treatment of adults and adolescents with perennial allergic rhinitis. Ann Allergy Asthma Immunol 2003;91:160-167.
57. Clinicaltrials.gov. Subcutaneous Omalizumab for Treatment of Chronic Rhinosinusitis with Nasal Polyposis (Xolair CRS). 2010. Available from
58. Clinicaltrials.gov. Xolair in Patients with Chronic Sinusitis. 2008. Available from
59. Kuehr J, et al. Efficacy of combination treatment with anti-IgE plus specific immunotherapy in polysensitized children and adolescents with seasonal allergic rhinitis. J Allergy Clin Immunol 2002;109:274-280.
60. Casale TB, et al. Omalizumab pretreatment decreases acute reactions after rush immunotherapy for ragweed-induced seasonal allergic rhinitis. J Allergy Clin Immunol 2006;117:134-140.
61. Massanari M, et al. Effect of pretreatment with omalizumab on the tolerability of specific immunotherapy in allergic asthma. J Allergy Clin Immunol 2010;125:383-389.
62. Clinicaltrials.gov. A Pilot Study of the Treatment of Eosinophilic Esophagitis with Omalizumab. 2010. Available from
63. Clinicaltrials.gov. Omalizumab to Treat Hyper-IgE (Job's) Syndrome. 2010. Available from
64. Clinicaltrials.gov. A Randomized, Double-Blind, Placebo-Controlled Study of Omalizumab for Idiopathic Anaphylaxis. 2010. Available from
65. Clinicaltrials.gov. Identifying Responders to Xolair (Omalizumab) Using Eosinophilic Esophagitis as a Disease Model. 2009. Available from
66. Clinicaltrials.gov. Omalizumab in the Treatment of Peanut Allergy. 2009. Available from
67. Clinicaltrials.gov. An Exploratory Study to Assess Multiple Doses of Omalizumab in Patients with Cystic Fibrosis Complicated by ABPA. 2010. Available from
68. Lane JE, Cheyney JM, Lane TN, Kent DE, Cohen DJ. Treatment of recalcitrant atopic dermatitis with omalizumab. J Am Acad Dermatol 2006;54:68-72.
69. Spector SL, Tan RA. Effect of omalizumab on patients with chronic urticaria. Ann Allergy Asthma Immunol 2007;99:190-193.
70. Clinicaltrials.gov. A Study of Xolair (Omalizumab) in Patients with Chronic Idiopathic Urticaria (CIU) Who Remain Symptomatic with Antihistamine Treatment (H1). 2010. Available from
71. Limb SL, Starke PR, Lee CE, Chowdhury BA. Delayed onset and protracted progression of anaphylaxis after omalizumab administration in patients with asthma. J Allergy Clin Immunol 2007;120:1378-1381.
72. Cox L, Platts-Mills TA, Finegold I, Schwartz LB, Simons FE, Wallace DV. American Academy of Allergy, Asthma and Immunology/American College of Allergy, Asthma and Immunology Joint Task Force Report on omalizumab-associated anaphylaxis. J Allergy Clin Immunol 2007;120:1373-1377.
73. Wechsler ME, Wong DA, Miller MK, Lawrence-Miyasaki L. Churg-strauss syndrome in patients treated with omalizumab. Chest 2009;136:507-518.
74. Poole JA, Meng J, Reff M, Spellman MC, Rosenwasser LJ. Anti-CD23 monoclonal antibody, lumiliximab, inhibited allergen-induced responses in antigen-presenting cells and T cells from atopic subjects. J Allergy Clin Immunol 2005;116:780-788.
75. Casale T, Busse W, Lizambri R. Results of a Phase II, multiple-dose, randomized trial of an anti-CD23 monoclonal antibody (IDEC-152) in patients with seasonal allergic rhinitis. J Allergy Clin Immunol 2003;111:S75.
76. Rosenwasser LJ, Busse WW, Lizambri RG, Olejnik TA, Totoritis MC. Allergic asthma and an anti-CD23 mAb (IDEC-152): results of a phase I, single-dose, dose-escalating clinical trial. J Allergy Clin Immunol 2003;112:563-570.
77. Pettipher R. The roles of the prostaglandin D(2) receptors DP(1) and CRTH2 in promoting allergic responses. Br J Pharmacol 2008;153(Suppl):S191-S199.
78. Barnes NB, et al. A randomised, double-blind, placebo-controlled study of the CRTH2 antagonist OC000459 on moderate persistent asthma. European Respiratory Society Annual Meeting 2009;29:???-???. Abstract 3267.
79. Clinicaltrials.gov. Proof of Concept Study of OC000459 in Eosinophilic Esophagitis. 2010. Available from
80. Carter LL, et al. Potent and selective CRTh2 antagonists are efficacious in models of asthma, allergic rhinitis and atopic dermatitis. J Allergy Clin Immunol 2010;5:AB490.
81. Clinicaltrials.gov. AMG 853 Phase 2 Study in Subjects with Inadequately Controlled Asthma. 2010. Available from
82. Rossi AB, et al. Identification of the Syk kinase inhibitor R112 by a human mast cell screen. J Allergy Clin Immunol 2006;118:749-755.
83. Meltzer EO, Berkowitz RB, Grossbard EB. An intranasal Syk-kinase inhibitor (R112) improves the symptoms of seasonal allergic rhinitis in a park environment. J Allergy Clin Immunol 2005;115:791-796.
84. Rigel Pharmaceuticals. Rigel Announces Disappointing Results from Phase II Study of R112 for the Treatment of Allergic Rhinitis. 2005. Available from
85. Gauvreau GM, et al. Antisense therapy against CCR3 and the common beta chain attenuates allergen-induced eosinophilic responses. Am J Respir Crit Care Med 2008;177:952-958.
86. Gauvreau G, et al. Efficacy of increasing doses of TPI ASM8 on allergen inhalation challenges in asthmatics. Am J Respir Crit Care Med 2010;181:????-????.
87. Fortin M, Moktefi K, Court M, Seguin S, Ferrari N. TPI ASM8, an inhaled antisense oligonucleotide drug candidate targeting CCR3 And The common beta chain of IL-3, IL-5 And GM-CSF receptors, potentiates the anti-inflammatory activity of an inhaled corticosteroid in a rat model of asthma. Am J Respir Crit Care Med 2010;181:????-????.
88. Clinicaltrials.gov. Efficacy of TPI ASM8 During a 14-Day Allergen Challenge. 2010. Available at:
89. Oldhoff JM, et al. Anti-IL-5 recombinant humanized monoclonal antibody (Mepolizumab) for the treatment of atopic dermatitis. Allergy 2005;60:693-696.
90. Straumann A, et al. Anti-interleukin-5 antibody treatment (Mepolizumab) in active eosinophilic oesophagitis: a randomised, placebo-controlled, double-blind trial. Gut 2010;59:21-30.
91. Haldar P, et al. Mepolizumab and exacerbations of refractory eosinophilic asthma. N Engl J Med 2009;360:973-984.
92. Nair P, et al. Mepolizumab for prednisone-dependent asthma with sputum eosinophilia. N Engl J Med 2009;360:985-993.
93. Walsh GM. Reslizumab, a humanized anti-IL-5 mAb for the treatment of eosinophil-mediated inflammatory conditions. Curr Opin Mol Ther 2009;11:329-336.
94. Clinicaltrials.gov. Open-Label Extension Study of Reslizumab in Pediatric Subjects with Eosinophilic Esophagitis. 2010. Available from
95. Kolbeck R, et al. MEDI-563, a humanized anti-IL-5 receptor alpha mAb with enhanced antibody-dependent cell-mediated cytotoxicity function. J Allergy Clin Immunol 2010;125:1344-1353. e2.
96. Busse WW, et al. Safety profile, pharmacokinetics, and biologic activity of MEDI-563, an anti-IL-5 receptor alpha antibody, in a phase I study of subjects with mild asthma. J Allergy Clin Immunol 2010;125:1237-1244. e2.
97. Krieg AM. Therapeutic potential of Toll-like receptor 9 activation. Nat Rev Drug Discov 2006;5:471-484.
98. Creticos PS, et al. Immunotherapy with a ragweed-Toll-like receptor 9 agonist vaccine for allergic rhinitis. N Engl J Med 2006;355:1445-1455.
99. Tulic MK, et al. Amb a 1-immunostimulatory oligodeoxynucleotide conjugate immunotherapy decreases the nasal inflammatory response. J Allergy Clin Immunol 2004;113:235-241.
100. Bernstein D, Segall N, Nayak A, Casale T, Korenblat P, Martins E. Safety and efficacy of the novel vaccine Tolamba in ragweed allergic adults, a dose finding study. J Allergy Clin Immunol 2007;119(Suppl):S78-S79.
101. Gauvreau GM, Hessel EM, Boulet L, Coffman RL, O'Byrne PM. Immunostimulatory sequences regulate interferon-inducible genes but not allergic airway responses. Am J Respir Crit Care Med 2006;174:15-20.
102. Senti G, et al. Use of A-type CpG oligodeoxynucleotides as an adjuvant in allergen-specific immunotherapy in humans: a phase I/IIa clinical trial. Clin Exp Allergy 2009;39:562-570.
103. Blaziene A, et al. CYT003-QbG10, a novel allergen-independent immunotherapy, shown to be safe and efficacious in placebo-controlled Phase II study. Ann Allergy Asthma Immunol 2008:A19:???-???.
104. Cytos. Placebo-controlled Phase II Study Shows CYT003-QbG10 is Safe and Efficacious for the Treatment of Allergic Asthma. 2010. Available from
105. Casale TB, Kessler J, Romero FA. Safety of the intranasal toll-like receptor 4 agonist CRX-675 in allergic rhinitis. Ann Allergy Asthma Immunol 2006;97:454-456.
106. Rosewich M, et al. Tolerance induction after specific immunotherapy with pollen allergoids adjuvanted by monophosphoryl lipid A in children. Clin Exp Immunol 2010;160:403-410.
107. Musarra A, Bignardi D, Troise C, Passalacqua G. Long-lasting effect of a monophosphoryl lipid-adjuvanted immunotherapy to parietaria. A controlled field study. Eur Ann Allergy Clin Immunol 2010;42:115-119.
108. Rosewich M. Ultra-short course immunotherapy in children and adolescents during a 3-years post-marketing surveillance study. Pediatr Allergy Immunol 2009;???:???-???.
109. Pfaar O, Barth C, Jaschke C, Hormann K, Klimek L. Sublingual allergen-specific immunotherapy adjuvanted with monophosphoryl lipid A: A Phase I/IIa study. Int Arch Allergy Immunol 2010;154:336-344.
110. VentiRx. VentiRx Pharmaceuticals Reports Positive Clinical Data for VTX-1463 in Allergic Rhinitis. 2010. Available from