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Anti-IL-4/IL-13 Biologics

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Asthma: Targeted Biological Therapies

Abstract

The recent advances in our understanding of asthma pathobiology can have relevant implications in both present and future therapeutic approaches. Within this context, the current more detailed knowledge of the key cellular and molecular mechanisms underlying asthma is unravelling potential targets such as IL-4 and IL-13 for the development and implementation of new biological therapies [1].

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References

  1. Walsh GM. Anti-IL-4/-13 based therapy in asthma. Expert Opin Emerg Drugs. 2015;20:349–52.

    Article  CAS  PubMed  Google Scholar 

  2. Steinke JW, Borish L. Th2 cytokines and asthma. Interleukin 4: its role in the pathogenesis of asthma, and targeting it for asthma treatment with interleukin-4 receptor antagonists. Respir Res. 2001;2:66–70.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Corren J. Role of interleukin-13 in asthma. Curr Allergy Asthma Rep. 2013;13:415–20.

    Article  CAS  PubMed  Google Scholar 

  4. Vatrella A, Fabozzi I, Calabrese C, et al. Dupilumab: a novel treatment for asthma. J Asthma Allergy. 2014;7:123–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Froidure A, Mouthuy J, Durham SR, et al. Asthma phenotypes and IgE responses. Eur Respir J. 2016;47:304–19.

    Article  CAS  PubMed  Google Scholar 

  6. Saha SK, Berry MA, Parker D, et al. Increased sputum and bronchial biopsy IL-13 expression in severe asthma. J Allergy Clin Immunol. 2008;121:685–91.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Corren J. Anti-interleukin-13 antibody therapy for asthma: one step closer. Eur Respir J. 2013;41:255–6.

    Article  CAS  PubMed  Google Scholar 

  8. Maes T, Joos GF, Brusselle GG. Targeting IL-4 in asthma: lost in translation? Am J Respir Cell Mol Biol. 2012;47:261–70.

    Article  CAS  PubMed  Google Scholar 

  9. Prieto J, Lensmar C, Roquet AI, et al. Increased interleukin-13 mRNA expression in bronchoalveolar lavage cells of atopic patients with mild asthma after repeated low-dose allergen provocations. Respir Med. 2000;94:806–14.

    Article  CAS  PubMed  Google Scholar 

  10. Howard TD, Koppelman GH, Xu J, et al. Gene-gene interaction in asthma: IL4RA and IL-13 in a Dutch population with asthma. Am J Hum Genet. 2002;70:230–6.

    Article  CAS  PubMed  Google Scholar 

  11. Li X, Howard TD, Zheng SL, et al. Genome-wide association study of asthma identifies RAD50-IL13 and HLA-DR/DQ regions. J Allergy Clin Immunol. 2010;125:328–35.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Wills-Karp M, Luyimbazi J, Xu X, et al. Interleukin-13: central mediator of allergic asthma. Science. 1998;282:2258–61.

    Article  CAS  PubMed  Google Scholar 

  13. Grunig G, Warnock M, Wakil AE, et al. Requirement for IL-13 independently of IL-4 in experimental asthma. Science. 1998;282:2261–3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Munitz A, Brandt EB, Mingler M, et al. Distinct roles for IL-13 and IL-4 via IL-13 receptor α1 and the type II IL-4 receptor in asthma pathogenesis. Proc Natl Acad Sci U S A. 2008;105:7240–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Kotsimbos TC, Ernst P, Hamid QA, et al. Interleukin-13 and interleukin-4 are coexpressed in atopic asthma. Proc Assoc Am Physicians. 1996;108:368–73.

    CAS  PubMed  Google Scholar 

  16. Oh CK, Geba GP, Molfino N. Investigational therapeutics targeting the IL-4/IL-13/STAT-6 pathway for the treatment of asthma. Eur Respir Rev. 2010;19:46–54.

    Article  CAS  PubMed  Google Scholar 

  17. Andrews R, Rosa L, Daines M, Khurana HG. Reconstitution of a functional human type II IL-4/IL-13 receptor in mouse B cells: demonstration of species specificity. J Immunol. 2001;166:1716–22.

    Article  CAS  PubMed  Google Scholar 

  18. Chiba Y, Goto K, Misawa M. Interleukin-13-induced activation of signal transducer and activator of transcription 6 is mediated by an activation of Janus kinase 1 in cultured human bronchial smooth muscle cells. Pharmacol Rep. 2012;64:454–8.

    Article  CAS  PubMed  Google Scholar 

  19. Zheng T, Liu W, Oh SY, et al. IL-13 receptor α2 selectively inhibits IL-13-induced responses in the murine lung. J Immunol. 2008;180:522–9.

    Article  CAS  PubMed  Google Scholar 

  20. Hart TK, Blackburn MN, Brigham-Burke M, et al. Preclinical efficacy and safety of pascolizumab (SB 240683): a humanized anti-interleukin-4 antibody with therapeutic potential in asthma. Clin Exp Immunol. 2002;130:93–100.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Pelaia G, Vatrella A, Maselli R. The potential of biologics for the treatment of asthma. Nat Rev Drug Discov. 2012;11:958–72.

    Article  CAS  PubMed  Google Scholar 

  22. Gallelli L, Busceti MT, Vatrella A, et al. Update on anti-cytokine treatment for asthma. Biomed Res Int. 2013;2013:104315.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Antoniu SA, Cojocaru I. Pitrakinra for asthma. Expert Opin Biol Ther. 2010;10:1609–15.

    Article  CAS  PubMed  Google Scholar 

  24. Burmeister Getz E, Fisher DM, Fuller R. Human pharmacokinetics/pharmacodynamics of an interleukin-4 and interleukin-13 dual antagonist in asthma. J Clin Pharmacol. 2009;49:1025–36.

    Article  CAS  PubMed  Google Scholar 

  25. Holgate ST. Pathophysiology of asthma: what has our current understanding taught us about new therapeutic approaches? J Allergy Clin Immunol. 2011;128:495–505.

    Article  CAS  PubMed  Google Scholar 

  26. Wenzel S, Wilbraham D, Fuller R, et al. 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;370:1422–31.

    Article  CAS  PubMed  Google Scholar 

  27. Slager RE, Otulana BA, Hawkins GA, et al. IL-4 receptor polymorphisms predict reduction in asthma exacerbations during response to an anti-IL-4 receptor α antagonist. J Allergy Clin Immunol. 2012;130:516–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Wenzel S, Ford L, Pearlman D, et al. Dupilumab in persistent asthma with elevated eosinophil levels. N Engl J Med. 2013;368:2455–66.

    Article  CAS  PubMed  Google Scholar 

  29. Wechsler ME. Inhibiting IL-4 and IL-13 in difficult-to-control asthma. N Engl J Med. 2013;368:2511–3.

    Article  CAS  PubMed  Google Scholar 

  30. Wenzel S, Castro M, Corren J, et al. Dupilumab efficacy and safety in adults with uncontrolled persistent asthma despite use of medium-to-high-dose inhaled corticosteroids plus a long-acting β2 agonist: a randomised double-blind placebo-controlled pivotal phase 2b dose-ranging trial. Lancet. 2016;388:31–44.

    Article  CAS  PubMed  Google Scholar 

  31. Spiess C, Bevers III J, Jackman J, et al. Development of a human IgG4 bispecific antibody for dual targeting of interleukin-4 (IL-4) and interleukin-13 (IL-13) cytokines. J Biol Chem. 2013;288:26583–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Ultsch M, Bevers J, Nakamura G, et al. Structural basis of signaling blockade by anti-IL-13 antibody lebrikizumab. J Mol Biol. 2013;425:1330–9.

    Article  CAS  PubMed  Google Scholar 

  33. Thomson NC, Patel M, Smith AD. Lebrikizumab in the personalized management of asthma. Biol. 2012;6:329–35.

    CAS  Google Scholar 

  34. Maselli DJ, Keyt H, Rogers L. Profile of lebrikizumab and its potential role in the treatment of asthma. J Asthma Allergy. 2015;8:87–92.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Li W, Gao P, Zhi Y, et al. Periostin: its role in asthma and its potential as a diagnostic or therapeutic target. Respir Res. 2015;16:57.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Takayama G, Arima K, Kanaji T, et al. Periostin: a novel component of subepithelial fibrosis of bronchial asthma downstream of IL-4 and IL-13 signals. J Allergy Clin Immunol. 2006;118:98–104.

    Article  CAS  PubMed  Google Scholar 

  37. Jia G, Erickson RW, Choy DF, et al. Periostin is a systemic biomarker of eosinophilic airway inflammation in asthmatic patients. J Allergy Clin Immunol. 2012;130:647–54.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Corren J, Lemanske RF, Hanania NA, et al. Lebrikizumab treatment in adults with asthma. N Engl J Med. 2011;365:1088–98.

    Article  CAS  PubMed  Google Scholar 

  39. McClintock D, Corren J, Hanania NA, et al. Lebrikizumab, an anti-IL-13 monoclonal antibody, reduces severe asthma exacerbations over 32 weeks in adults with inadequately controlled asthma. Int Conf Am Thorac Soc. (May 18–23, San Francisco), Abst 813, 2012.

    Google Scholar 

  40. Noonan M, Korenblat P, Mosesova S, et al. Dose-ranging study of lebrikizumab in asthmatic patients not receiving inhaled steroids. J Allergy Clin Immunol. 2013;132:567–74.

    Article  CAS  PubMed  Google Scholar 

  41. Scheerens H, Arron JR, Zheng Y, et al. The effects of lebrikizumab in patients with mild asthma following whole lung allergen challenge. Clin Exp Allergy. 2014;44:38–46.

    Article  CAS  PubMed  Google Scholar 

  42. Hanania NA, Noonan M, Corren J, et al. Lebrikizumab in moderate-to-severe asthma: pooled data from two randomised placebo-controlled studies. Thorax. 2015;70:748–56.

    Article  PubMed  PubMed Central  Google Scholar 

  43. Blanchard C, Mishra A, Saito-Hakei H, et al. Inhibition of human interleukin-13-induced respiratory and oesophageal inflammation by anti-human interleukin-13 antibody (CAT-354). Clin Exp Allergy. 2005;35:1096–103.

    Article  CAS  PubMed  Google Scholar 

  44. Walsh GM. Tralokinumab, an anti-IL-13 mAb for the potential treatment of asthma and COPD. Curr Opin Invest Drugs. 2010;11:1305–12.

    CAS  Google Scholar 

  45. Antohe I, Croitoru R, Antoniu S. Tralokinumab for uncontrolled asthma. Exp Opin Biol Ther. 2013;13:323–6.

    Article  CAS  Google Scholar 

  46. Piper E, Brightling C, Niven R, et al. A phase II placebo-controlled study of tralokinumab in moderate-to-severe asthma. Eur Respir J. 2013;41:330–8.

    Article  CAS  PubMed  Google Scholar 

  47. Brightling CE, Chanez P, Leigh R, et al. Efficacy and safety of tralokinumab in patients with severe uncontrolled asthma: a randomised, double-blind, placebo-controlled, phase 2b trial. Lancet Respir Med. 2015;3:692–701.

    Article  CAS  PubMed  Google Scholar 

  48. Lun SW, Wong CK, Ko FW, et al. Increased expression of plasma and CD4+ T lymphocyte costimulatory molecule CD26 in adult patients with allergic asthma. J Clin Immunol. 2007;27:430–7.

    Article  CAS  PubMed  Google Scholar 

  49. Hodsman P, Ashman C, Cahn A, et al. A phase 1, randomized, placebo-controlled study of an anti-IL-13 monoclonal antibody in healthy subjects and mild asthmatics. Br J Clin Pharmacol. 2012;75:118–28.

    Article  CAS  PubMed Central  Google Scholar 

  50. De Boever EH, Ashman C, Cahn AP, et al. Efficacy and safety of an anti-IL-13 mAB in patients with severe asthma: a randomized trial. J Allergy Clin Immunol. 2014;133:989–96.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. University “Magna Graecia”, Catanzaro, Italy

    Girolamo Pelaia & Rosario Maselli

  2. University of Salerno, Salerno, Italy

    Alessandro Vatrella

Authors
  1. Girolamo Pelaia
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  2. Alessandro Vatrella
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  3. Rosario Maselli
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Pelaia, G., Vatrella, A., Maselli, R. (2017). Anti-IL-4/IL-13 Biologics. In: Asthma: Targeted Biological Therapies. Springer, Cham. https://doi.org/10.1007/978-3-319-46007-9_6

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  • DOI: https://doi.org/10.1007/978-3-319-46007-9_6

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  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-46005-5

  • Online ISBN: 978-3-319-46007-9

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