Intralymphatic immunotherapy for cat allergy induces tolerance after only 3 injections - 28/04/12
Corresponding author: Thomas M. Kündig, MD, Department of Dermatology, University Hospital Zurich, Gloriastrasse 31, 8091 Zurich.Abstract |
Background |
Subcutaneous allergen-specific immunotherapy frequently causes allergic side effects and requires 30 to 80 injections over 3 to 5 years.
Objective |
We sought to improve immunotherapy by using intralymphatic allergen administration (intralymphatic immunotherapy [ILIT]) and by targeting allergen to the MHC class II pathway.
Methods |
Recombinant major cat dander allergen Fel d 1 was fused to a translocation sequence (TAT) and to part of the human invariant chain, generating a modular antigen transporter (MAT) vaccine (MAT–Fel d 1). In a randomized double-blind trial ILIT with MAT–Fel d 1 in alum was compared with ILIT with placebo (saline in alum) in allergic patients (ClinicalTrials.gov NCT00718679).
Results |
ILIT with MAT–Fel d 1 elicited no adverse events. After 3 placebo injections within 2 months, nasal tolerance increased less than 3-fold, whereas 3 intralymphatic injections with MAT–Fel d 1 increased nasal tolerance 74-fold (P < .001 vs placebo). ILIT with MAT–Fel d 1 stimulated regulatory T-cell responses (P = .026 vs placebo) and increased cat dander–specific IgG4 levels by 5.66-fold (P = .003). The IgG4 response positively correlated with IL-10 production (P < .001).
Conclusion |
In a first-in-human clinical study ILIT with MAT–Fel d 1 was safe and induced allergen tolerance after 3 injections.
Le texte complet de cet article est disponible en PDF.Key words : Intralymphatic, cat dander allergy, immunotherapy, tolerance, vaccination, Fel d 1
Abbreviations used : IDT, ILIT, MAT, mRQLQ, NPT, SIT, SPT
Plan
| Supported by ImVisioN Therapeutics AG and the Swiss National Science Foundation. H.R. and M.S. are employees of ImVisioN Therapeutics AG. T.M.K., R.C., and H.G. are scientific advisors for and receive travel expenses from ImVisioN GmbH. |
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| Disclosure of potential conflict of interest: M. Steiner and H. Rose are employed by ImVisioN GmbH. L. A. Hothorn has received research support from ImVisioN GmbH and the Center for Clinical Research, University Hospital Zurich. C. A. Akdis receives research support from Novartis, PREDICTA, the Swiss National Science Foundation, MeDALL, the Global Allergy and Asthma European Network, and the Christine Kühne Center for Allergy Research and Education; has consulted for Actelion, Aventis, Stallergenes, and Allergopharma; is President of the European Academy of Allergy and Clinical Immunology; is a fellow and interest group member of the American Academy of Allergy, Asthma & Immunology; is a former committee member of the Global Allergy and Asthma European Network; and is director of the Christine Kühne Center for Allergy Research and Education. M. Akdis has received research support from the Swiss National Foundation and the European Union. The rest of the authors declare that they have no relevant conflicts of interest. |
Vol 129 - N° 5
P. 1290-1296 - mai 2012 Retour au numéro
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