TY - JOUR

T1 - Intralymphatic immunotherapy for cat allergy induces tolerance after only 3 injections

AU - Senti, Gabriela

AU - Crameri, Reto

AU - Kuster, Daniela

AU - Johansen, Pål

AU - Martinez-Gomez, Julia M.

AU - Graf, Nicole

AU - Steiner, Martin

AU - Hothorn, Ludwig A.

AU - Grönlund, Hans

AU - Tivig, Christine

AU - Zaleska, Anna

AU - Soyer, Ozge

AU - Van Hage, Marianne

AU - Akdis, Cezmi A.

AU - Akdis, Mübeccel

AU - Rose, Horst

AU - Kündig, Thomas M.

N1 - Funding Information: 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. 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.

PY - 2012/3/30

Y1 - 2012/3/30

N2 - 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 IgG 4 levels by 5.66-fold (P =.003). The IgG 4 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.

AB - 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 IgG 4 levels by 5.66-fold (P =.003). The IgG 4 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.

KW - cat dander allergy

KW - Fel d 1

KW - immunotherapy

KW - Intralymphatic

KW - tolerance

KW - vaccination

UR - http://www.scopus.com/inward/record.url?scp=84860486360&partnerID=8YFLogxK

U2 - 10.1016/j.jaci.2012.02.026

DO - 10.1016/j.jaci.2012.02.026

M3 - Article

C2 - 22464647

AN - SCOPUS:84860486360

VL - 129

SP - 1290

EP - 1296

JO - Journal of Allergy and Clinical Immunology

JF - Journal of Allergy and Clinical Immunology

SN - 0091-6749

IS - 5

ER -