Anti-IgE therapy combined with SIT: contra.
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Antibodies, Monoclonal↗
Biomedical subjects
Mark Larché
Publications and source records attributed to Mark Larché.
The potential of peptide immunotherapy in allergy and asthma.
Allergic conditions contribute significantly to the burden of chronic disease in the industrialized world. Current treatments offer varying degrees of palliation. The sole proven disease-modifying strategy, specific or whole-allergen immunotherapy, is limited because of the associated risk of systemic adverse effects, such as anaphylaxis. Short, linear allergen-derived peptides, corresponding to T cell epitopes, offer the possibility of a safer approach as they are capable of inducing allergen-specific hyporesponsiveness without cross-linking mast cell-bound IgE. This review evaluates the scientific basis of peptide immunotherapy and clinical experience in allergy up to the present time.
Animals↗
Peptide-based vaccines in the treatment of specific allergy.
The efficacy of conventional allergen-specific immunotherapy (SIT) for allergic conditions and venom hypersensitivity is well documented. However it's use is limited due allergic side effects including anaphylaxis and the difficulty of standardising proteins in complex allergenic mixtures. The aim of new therapeutic strategies is to circumvent these limitations and approaches include allergen non-specific therapy, such as anti-IgE and anti-cytokine therapy and other allergen specific techniques including the peptide based vaccines (PBV), modified allergens (allergoids) and DNA vaccines. PBV are small linear peptide fragments containing T cell epitopes which are designed to reduce the ability to cross link antigen-specific IgE. Studies in animal models have confirmed proof of principle demonstrating the induction of hyporesponsiveness using high doses of peptides. However, the principle limitation to clinical use of PBV is the polymorphism of HLA class II molecules. There are ongoing clinical studies using peptide-based vaccines for cat, bee and grass allergies--looking at both immunological mechanisms and clinical outcome measures. The mechanisms underlying the efficacy of PBV appear to be similar to those described for classical immunological tolerance. Thus, the peptides may induce anergy due to absence of co-stimulation, activation-induced cell death, a switch from a Th2 to a Th1 cytokine profile, the induction of regulatory T cells or combinations of these mechanisms. Successful immunotherapy, in bee sensitive individuals, is associated with the elaboration of IL-10. Clonal deletion is unlikely as an overall mechanism as there is evidence that the subsequent in vitro response to associated, non-injected, peptides can be suppressed. Mechanistic studies continue to provide insight into the mode of action of whole allergen and peptide-based immunotherapy. Clinical studies designed on the basis of these observations hold the promise of safer vaccines with improved efficacy. Whether this strategy can be used for allergy to complex allergen mixtures such as dust mites will need further evaluation.
Allergens↗