Fel d 1–derived peptide antigen desensitization shows a persistent treatment effect 1 year after the start of dosing: A randomized, placebo-controlled study

Patel, Deepen; Couroux, Peter; Hickey, Pascal; Salapatek, Anne Marie; Laidler, Paul; Larché, Mark; Hafner, Roderick P.

doi:10.1016/j.jaci.2012.07.028

Cited by 182 publications

(146 citation statements)

References 19 publications

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“…In light of this study, it is interesting to speculate on how currently favored regimes for delivering allergen immunotherapy, for example multidose regimes (17,20,53,54), affect the dynamics of CD62L expression of Th2 cells and hence their behavior in re- sponse to PIT. Here we used a single PIT protocol known to be effective against naive OT-II T cells and found it had limited efficacy in preventing pathogenic activity of Tcm.…”

Section: Discussionmentioning

confidence: 99%

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Effector and central memory T helper 2 cells respond differently to peptide immunotherapy

Mackenzie

Nowakowska

Leech

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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Peptide immunotherapy (PIT) offers realistic prospects for the treatment of allergic diseases, including allergic asthma. Much is understood of the behavior of naive T cells in response to PIT. However, treatment of patients with ongoing allergic disease requires detailed understanding of the responses of allergenexperienced T cells. CD62L expression by allergen-experienced T cells corresponds to effector/effector memory (CD62L lo ) and central memory (CD62L hi ) subsets, which vary with allergen exposure (e.g., during, or out with, pollen season). The efficacy of PIT on different T helper 2 (Th2) cell memory populations is unknown. We developed a murine model of PIT in allergic airway inflammation (AAI) driven by adoptively transferred, traceable ovalbumin-experienced Th2 cells. PIT effectively suppressed AAI driven by unfractionated Th2 cells. Selective transfer of CD62L hi and CD62L lo Th2 cells revealed that these two populations behaved differently from one another and from previously characterized (early deletional) responses of naive CD4 + T cells to PIT. Most notably, allergen-reactive CD62L lo Th2 cells were long-lived within the lung after PIT, before allergen challenge, in contrast to CD62L hi Th2 cells. Despite this, PIT was most potent against CD62L lo Th2 cells in protecting from AAI, impairing their ability to produce Th2 cytokines, whereas this capacity was heightened in PIT-treated CD62L hi Th2 cells. We conclude that Th2 cells do not undergo an early deletional form of tolerance after PIT. Moreover, memory Th2 subsets respond differently to PIT. These findings have implications for the clinical translation of PIT in different allergic scenarios.

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Section: Discussionmentioning

confidence: 99%

“…Encouraging findings have also been reported in allergic patients (16)(17)(18)(19)(20). However, reduced disease severity is not universal, and limitations in our understanding of the workings of PIT are impeding clinical translation.…”

mentioning

confidence: 99%

Effector and central memory T helper 2 cells respond differently to peptide immunotherapy

Mackenzie

Nowakowska

Leech

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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“…Similar results were observed at the 18-to 22-week posttreatment follow-up. Additionally, identical EEC evaluations at 50-54 weeks posttreatment demonstrated significant reduction in TRSS compared with the group treated with placebo, despite 9 months without treatment (10). In a protocol extension with blinding maintained, volunteers were also evaluated at the 2-year time point (100-104 wk) by EEC exposure.…”

Section: Clinical Efficacy Of Peptide Immunotherapymentioning

confidence: 99%

Mechanisms of Peptide Immunotherapy in Allergic Airways Disease

Larché

2014

Annals ATS

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Allergen immunotherapy with whole proteins is clinically efficacious but requires a protracted treatment period because of frequent allergic adverse events. A combination of duration of treatment and adverse events leads to poor compliance. Short synthetic peptides containing the major immunodominant T cell epitopes of allergenic proteins have been shown to reduce IgE cross-linking ability, thereby leading to fewer allergic adverse events following their administration to patients with allergies. Peptide immunotherapy has been shown to result in clinically meaningful efficacy in several Phase II, randomized, double-blind, placebo-controlled clinical trials. Exactly how peptide immunotherapy achieves its efficacy remains incompletely understood, but the mechanisms are thought to include immune deviation and induction of regulatory T cells capable of suppressing allergen-specific immune responses. Limited data are available on the effects of peptide therapy on humoral immune responses. Induction of allergen-specific IgG has been observed after peptide therapy, but the levels of antibody induced were much lower than generally seen with the utilization of whole allergen approaches. Thus, the immunological mechanisms of peptide immunotherapy appear to overlap, although not completely, with those seen in whole allergen therapy. Further studies are required to fully elucidate mechanisms of action.

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“…A significant reduction in symptoms, measured as the total rhinoconjunctivitis symptom score (TRSS), was observed following the administration of only eight intradermal injections of the peptide formulation. In this study, TRSS levels remained suppressed both at the 1-and 2-year follow-up time point [51]. The immunological mechanisms by which peptide immunotherapy induces tolerance are not yet fully understood.…”

Section: Peptide Immunotherapymentioning

confidence: 48%

Strategies to Study T Cells and T Cell Targets in Allergic Disease

Schulten¹

2017

Allergen

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Type I allergy is an immunoglobulin E (IgE)-mediated chronic disease. As such, disease diagnosis and identification of targeted allergens are primarily based on specific IgE reactivity. Over the past decades, the contribution of T cells in allergy pathogenesis has been extensively studied. T cells are not only significant for the onset and maintenance of allergic disease but likely also play a key role for the induction of tolerance by allergen-specific immunotherapy (AIT). Due to the complexity of allergic T cell responses, epitopes have only been thoroughly mapped for the most dominant and prevalent allergens. Recently developed laboratory approaches enable us to perform thorough peptide screens, identifying T cell epitopes in known and novel allergenic targets, irrespective of their IgE reactivity. Monitoring allergen-specific T cells and their phenotype will provide insights into disease manifestation and progression on a molecular level.However, performing such experiments in the clinic is not feasible. The definition of dominant T cell epitopes will allow us to create a tool to assess allergen-specific T cells in the context of different disease severities, such as rhinitis, asthma, and/or immunotherapy which will likely hold the key for improved diagnostic, biomarkers, and even novel therapeutic approaches.

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Fel d 1–derived peptide antigen desensitization shows a persistent treatment effect 1 year after the start of dosing: A randomized, placebo-controlled study

Abstract: A short course of Cat-PAD improves the ocular and nasal components of rhinoconjunctivitis symptoms in subjects with cat allergy, with the treatment effect persisting 1 year after the start of treatment.

Cited by 182 publications

References 19 publications

Effector and central memory T helper 2 cells respond differently to peptide immunotherapy

Effector and central memory T helper 2 cells respond differently to peptide immunotherapy

Mechanisms of Peptide Immunotherapy in Allergic Airways Disease

Strategies to Study T Cells and T Cell Targets in Allergic Disease

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