Allergen-related approaches to immunotherapy.

Allergic diseases, including asthma, rhinitis and eczema, represent a major health burden worldwide. Mainstay treatments are allergen avoidance where feasible and pharmacotherapy for symptom relief. For selected 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 or increasingly sublingually. However, application of this potentially curative treatment is restricted, largely due to the risk of serious adverse events, especially in asthmatics and for potent allergens such as peanut, seafood and latex. New insights into immunological mechanisms underlying effective SIT and molecular characterization of allergens and their recognition by the immune system suggest strategies for refinement of SIT. Selective targeting of allergen-specific T cells, especially regulatory T cells, is likely to be pivotal for efficacy. Recombinant allergens lacking IgE reactivity and small T cell epitope-based peptides are being trialled clinically with evidence of efficacy without serious IgE-mediated adverse reactions. Adjuvants, either co-administered or incorporated into a recombinant allergen vaccine to target tolerogenic dendritic cells may also increase efficacy. The safer sublingual route of allergen administration is attracting interest and different allergen forms may be optimal for inducing tolerance by this route. Defined allergen-derived molecules or peptides offer ease of standardization and, coupled with appropriate targeting of immunoregulatory mechanisms, will result in more widespread clinical use of SIT. Adjunct therapies such as anti-IgE antibody and corticosteroids may minimize the likelihood of adverse reactions in those with severe allergic disease who would most benefit from this treatment.