title: New approaches to transcutaneous immunotherapy: targeting dendritic cells with novel allergen conjugates.
abstract: OBJECTIVE
  This review summarizes recent preclinical and human studies evaluating allergen-specific immunotherapy via the transcutaneous route, and provides a rationale for the application of modified allergens with reduced allergenicity. Furthermore, it covers approaches to generate hypoallergenic conjugates for specific dendritic cell targeting.
  
  
  RESULTS
  Efficacy and safety of specific immunotherapy by application of allergens to the skin have been demonstrated in both animal models as well as clinical trials. However, localized adverse events have been reported, and delivery of antigens via barrier-disrupted skin has been linked to the induction of unwanted T helper 2-biased immune responses and allergic sensitization. Coupling of carbohydrates to allergens has been shown to induce formation of nanoparticles, which can specifically target dendritic cells and potentiate immune responses, and by masking B-cell epitopes, can render the molecules hypoallergenic.
  
  
  CONCLUSIONS
  Due to its abundance of immunocompetent cells, the skin represents an attractive target tissue for novel and enhanced immunotherapeutic approaches. However, in order to avoid adverse events and therapy-induced sensitizations, transcutaneous immunotherapy requires the use of formulations with reduced allergenic potential. Combining novel hypoallergenic conjugates with painless transcutaneous immunization techniques may provide an efficient and patient-friendly alternative to the standard specific immunotherapy practices.
authors.affiliation: Division of Allergy and Immunology, Department of Molecular Biology, University of Salzburg, Salzburg, Austria.
authors.forename: Richard
authors.initials: R
authors.lastname: Weiss
authors.forename: Sandra
authors.initials: S
authors.lastname: Scheiblhofer
authors.forename: Yoan
authors.initials: Y
authors.lastname: Machado
authors.forename: Josef
authors.initials: J
authors.lastname: Thalhamer
mesh_terms: D000485:Allergens / Q000276:immunology / Q000627:therapeutic use*; D003713:Dendritic Cells / Q000276:immunology*; D003888:Desensitization, Immunologic / Q000379:methods*; D016503:Drug Delivery Systems / Q000379:methods*; D018985:Epitopes, B-Lymphocyte / Q000276:immunology / Q000627:therapeutic use*; D006967:Hypersensitivity / Q000276:immunology / Q000628:therapy*; D007114:Immunization / Q000379:methods*
chemical_list: D000485:Allergens; D018985:Epitopes, B-Lymphocyte