Associate editor: P. FosterAllergen-related approaches to immunotherapyJennifer M. Rolland ?, Leanne M. Gardner, Robyn E. O'HehirDepartment ofImmunology, Monash University, Commercial Road, Melbourne Vic 3004, AustraliaDepartment ofAllergy, Immunology and Respiratory Medicine, Alfred Hospital, Melbourne, Victoria, Australiaa b s t r a c ta r t i c l ei n f oKeywords:AllergenAllergyAllergen immunotherapyRegulatory T cellsDendritic cellsAllergic diseases, including asthma, rhinitis and eczema, represent a major health burden worldwide.Mainstay treatments are allergen avoidance where feasible and pharmacotherapy for symptom relief. Forselected patients, allergen-specific immunotherapy (SIT) offers the prospect of long lasting clinical efficacy.SIT involves the administration of allergen extract using a standardized regimen, usually subcutaneously orincreasingly sublingually. However, application ofthis potentially curative treatment is restricted, largely dueto the risk ofserious adverse events, especially in asthmatics and for potent allergens such as peanut, seafoodand latex. New insights into immunological mechanisms underlying effective SIT and molecularcharacterization of allergens and their recognition by the immune system suggest strategies for refinementof SIT. Selective targeting of allergen-specific T cells, especially regulatory T cells, is likely to be pivotal forefficacy. Recombinant allergens lacking IgE reactivity and small T cell epitope-based peptides are beingtrialled clinically with evidence ofefficacy without serious IgE-mediated adverse reactions. Adjuvants, eitherco-administered or incorporated into a recombinant allergen vaccine to target tolerogenic dendritic cells mayalso increase efficacy. The safer sublingual route ofallergen administration is attracting interest and differentallergen forms may be optimal for inducing tolerance by this route. Defined allergen-derived molecules orpeptides offer ease of standardization and, coupled with appropriate targeting of immunoregulatorymechanisms, will result in more widespread clinical use of SIT. Adjunct therapies such as anti-IgE antibodyand corticosteroids may minimize the likelihood of adverse reactions in those with severe allergic diseasewho would most benefit from this treatment.© 2008 Elsevier Inc. All rights reserved.Contents1.2.3.4.5.Acknowledgments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Introduction. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Allergen-specific immunotherapy. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Mechanisms of specific immunotherapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .New approaches to allergen immunotherapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .2732742752782812812811. IntroductionAllergic diseases including asthma, rhinitis/conjunctivitis andeczema affect up to one quarter of the population in Westerncountries at some time in their lives and the prevalence is rising(Asheret al., 2006; Floistrup et al., 2006). The socioeconomic impactofthese diseases on the community is large, including costs of healthcare and lost work and school hours (Masoli et al., 2004). Allergicdiseases mainly affect atopic individuals, who have an inheritedgenetic predisposition to synthesize specific immunoglobulin E (IgE)Pharmacology & Therapeutics 121 (2009) 273–284Abbreviations: APC, antigen presenting cell; DC, dendritic cell; HDM, house dust mite; IgE, immunoglobulin E; IL, interleukin; MHC, major histocompatibility complex; PBMC,peripheral blood mononuclear cells; PRR, pattern recognition receptors; SCIT, subcutaneous allergen-specific immunotherapy; SIT, allergen-specific immunotherapy; SLIT, sublingualallergen-specific immunotherapy; TLR, Toll-like receptor; Tregs, regulatory T cells.? Corresponding author. Department of Immunology, Monash University, Commercial Road, Melbourne Vic 3004, Australia. Tel.: +61 3 9903 0480; fax: +61 3 9903 0038.E-mail address: jennifer.rolland@med.monash.edu.au (J.M. Rolland).0163-7258/$ – see front matter © 2008 Elsevier Inc. All rights reserved.doi:10.1016/j.pharmthera.2008.11.007Contents lists available at ScienceDirectPharmacology & Therapeuticsjournal homepage: www. el sevier. com/l ocate/pharmthera
