New Approaches to Transcutaneous Immunotherapy
New Approaches to Transcutaneous Immunotherapy
Purpose of review 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.
Recent findings 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.
Summary 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.
Despite the proven clinical efficacy of standard allergen-specific immunotherapy (SIT) performed by subcutaneous injection (SCIT) or sublingual application (SLIT), only a small percentage of allergic patients decide to undergo this laborious and time-consuming procedure, and dropout rates are considerable. Alternative approaches aiming at enhanced efficacy to reduce treatment duration and number of interventions, while simultaneously providing a high-safety profile, are under intense investigation. Among these, intranodal and cutaneous administration of allergens represent the most promising routes. This article provides an overview on experimental approaches for allergen immunotherapy via the cutaneous route (see Table 1). Furthermore, modifications of allergens for targeting specific receptors on antigen-presenting cells (APC), their implications for shaping the immune response, and the generation of hypoallergenic allergen conjugates are discussed.
Abstract and Introduction
Abstract
Purpose of review 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.
Recent findings 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.
Summary 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.
Introduction
Despite the proven clinical efficacy of standard allergen-specific immunotherapy (SIT) performed by subcutaneous injection (SCIT) or sublingual application (SLIT), only a small percentage of allergic patients decide to undergo this laborious and time-consuming procedure, and dropout rates are considerable. Alternative approaches aiming at enhanced efficacy to reduce treatment duration and number of interventions, while simultaneously providing a high-safety profile, are under intense investigation. Among these, intranodal and cutaneous administration of allergens represent the most promising routes. This article provides an overview on experimental approaches for allergen immunotherapy via the cutaneous route (see Table 1). Furthermore, modifications of allergens for targeting specific receptors on antigen-presenting cells (APC), their implications for shaping the immune response, and the generation of hypoallergenic allergen conjugates are discussed.
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