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Targeting the MHC class II pathway of antigen presentation enhances immunogenicity and safety of allergen immunotherapy.

AbstractBACKGROUND:
Current s.c. allergen-specific immunotherapy (SIT) leads to amelioration of IgE-mediated allergy, but it requires numerous allergen injections over several years and is frequently associated with severe side-effects. The aim of this study was to test whether modified recombinant allergens can improve therapeutic efficacy in SIT while reducing allergic side-effects.
METHODS:
The major cat allergen Fel d 1 was fused to a TAT-derived protein translocation domain and to a truncated invariant chain for targeting the MHC class II pathway (MAT-Fel d 1). The immunogenicity was evaluated in mice, while potential safety issues were assessed by cellular antigen stimulation test (CAST) using basophils from cat-dander-allergic patients.
RESULTS:
MAT-Fel d 1 enhanced induction of Fel d 1-specific IgG2a antibody responses as well as the secretion of IFN-gamma and IL-2 from T cells. Subcutaneous allergen-specific immunotherapy of mice using the modified Fel d 1 provided stronger protection against anaphylaxis than SIT with unmodified Fel d 1, and MAT-Fel d 1 caused less degranulation of human basophils than native Fel d 1.
CONCLUSION:
MAT-Fel d 1 allergen enhanced protective antibody and Th1 responses in mice, while reducing human basophil degranulation. Immunotherapy using MAT-Fel d 1 allergen therefore has the potential to enhance SIT efficacy and safety, thus, shortening SIT. This should increase patient compliance and lower treatment costs.
AuthorsJ M Martínez-Gómez, P Johansen, H Rose, M Steiner, G Senti, C Rhyner, R Crameri, T M Kündig
JournalAllergy (Allergy) Vol. 64 Issue 1 Pg. 172-8 (Jan 2009) ISSN: 1398-9995 [Electronic] Denmark
PMID19076537 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Allergens
  • Glycoproteins
  • Histocompatibility Antigens Class II
  • Recombinant Proteins
  • Fel d 1 protein, Felis domesticus
Topics
  • Allergens (therapeutic use)
  • Animals
  • Antibody Formation (drug effects)
  • Antigen Presentation
  • Basophils
  • Cats
  • Cell Degranulation (drug effects)
  • Drug Delivery Systems
  • Drug-Related Side Effects and Adverse Reactions
  • Glycoproteins (pharmacology, therapeutic use)
  • Histocompatibility Antigens Class II (metabolism)
  • Humans
  • Immunotherapy (methods)
  • Mice
  • Recombinant Proteins
  • Th1 Cells

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