Intralymphatic Immunotherapy: Update and Unmet Needs

Senti, Gabriela; Freiburghaus, Andreas U.; Larenas‐Linnemann, Désirée; Hoffmann, Hans‐Jürgen; Patterson, Alan; Klimek, Ludger; Bona, Danilo Di; Pfaar, Oliver; Ahlbeck, Lars; Akdiş, Mübeccel; Weinfeld, Dan; Contreras-Verduzco, Francisco Alberto; Pedroza-Meléndez, A; Skaarup, Søren Helbo; Lee, Sang Min; Cardell, Lars Olaf; Schmid, Johannes Martin; Westin, Ulla; Dollner, Ralph; Kündig, Thomas M.

doi:10.1159/000493647

Cited by 84 publications

(64 citation statements)

References 33 publications

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“…Throughout the text, SLIT will indicate the sublingual‐swallow modality. To conclude this general summary of the historical aspects, and for completeness, it has to be mentioned that in the last decade two new noninjection routes were proposed: the intralymphatic immunotherapy (ILIT) and the epicutaneous immunotherapy (EPIT), which are currently under development . A summary of the historical development of SLIT is depicted in Figure , and the main milestones are summarized in Table .…”

Section: Far History and Clinical Contextmentioning

confidence: 99%

30 years of sublingual immunotherapy

Passalacqua

Bagnasco

Canonica

2019

Allergy

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Allergen Immunotherapy (AIT) was introduced in clinical practice on an empirical basis more than 100 years ago. Since the first attempts, AIT was administered subcutaneously. Indeed, other routes of administration were proposed and studied, in particular to improve the safety, but only the sublingual route (SLIT) achieved a credibility based on evidence and was then accepted as a viable “alternative” option to the subcutaneous route. SLIT was largely used in clinical trials and clinical practice in this last 30 years. Thus, a large amount of data is available, coming from either controlled trials and postmarketing surveillance studies. It is clear that SLIT is overall effective, but it is also clear that the efficacy is not “class‐related,” as derived from meta‐analyses, but restricted to each specific product. The 30‐year lasting use of SLIT allowed to clarify many clinical aspects, such as efficacy, safety, use in asthma, regimens of administration, and optimal doses. In parallel, the mechanisms of action of AIT were elucidated, and new indications were proposed (eg food allergy, atopic dermatitis). In addition, the introduction of molecular‐based diagnosis, allowed to better refine the prescription of SLIT, based on specific sensitization profiles. The present article will describe the origin and evolution of SLIT for respiratory allergy, taking into account the clinical context that suggested this form of treatment, the recently developed aspects, the future perspectives and unmet needs, This is not, therefore, a systematic review, rather a narrative historical description of the past history, and a look forward to the future opportunities.

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Section: Far History and Clinical Contextmentioning

confidence: 99%

30 years of sublingual immunotherapy

Passalacqua

Bagnasco

Canonica

2019

Allergy

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“…It also has a reduced risk of systemic adverse effects, such as anaphylaxis that can have fatal consequences. This novel route of administration is promising but more clinical data is necessary to approve the routine use of ILIT [22].…”

Section: General Methods and Novel Approaches Of Administrationmentioning

confidence: 99%

“…In a novel approach with major cat allergen Feld1 has demonstrated that after intralymphatic immunotherapy with recombinant MAT-Feld1 in a human, a predominant subclass of IgG was observed as IgG4 instead of IgG, IgG2 and IgG3 [38]. T cell unresponsiveness to allergen identified by increased allergen-specific IL-10-producing FOXP3 positive Tregs [22].…”

Section: Ilit Mechanismsmentioning

confidence: 99%

Diverse Mechanisms of Allergen Specific Immunotherapy

Cevhertas

Лацин

Akdiş

et al. 2019

Vestn. Ross. univ. družby nar., Ser. Med.

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Allergen immunotherapy (AIT) is widely used to establish a tolerant immune response and it is currently the only disease modifying treatment. There are different routes to administer the allergen, including subcutaneous, sublingual, intralymphatic, epicutaneous, intradermal, and oral and local nasal allergen immunotherapy. Although the optimal administration route depends on the type of allergen, some patients remain unresponsive and so it is important to predict the outcome before and during treatment. Therefore, there is a need to identify candidate prognostic markers for allergen immunotherapy. Herein, we discuss the recent literature on the molecular mechanisms of AIT.

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“…Although few ILIT randomized controlled clinical trials were published to date (reviewed in Ref. ), the clinical data showed that short‐course ILIT reduced the risk of systemic adverse effects and improved clinical symptoms with the same efficiency than three to five years of conventional SCIT. These promising efficacy data need to be consolidated through more clinical trials to evaluate ILIT long‐term effects.…”

Section: New Routes For Aitmentioning

confidence: 99%

Molecular approaches to allergen‐specific immunotherapy: Are we so far from clinical implementation?

Pechsrichuang

Jacquet

2020

Clin Experimental Allergy

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Conventional allergen-specific immunotherapy (AIT), based on administrations of allergen extracts, represents up to now the unique protocol for the desensitization of allergic patients. Whereas the effectiveness of AIT was evidenced for the treatment of allergic rhinitis and allergic asthma, such strategy remains experimental for food allergies up to now. However, important issues are commonly associated with AIT as the quality of natural allergen extracts, the long duration and adverse side-effects which negatively affect successful desensitization together with the patient compliance. The rapid progression of molecular allergology made possible the quest of safer, shorter and more effective immunotherapeutic approaches. The aim of this review was to provide an update on these different innovative recombinant derivatives including their efficacy but also their limitations. Despite promising preclinical and early clinical studies, the absence of convincing data in large phase III trials precludes so far the translation of these immunotherapeutic candidates into the clinic. K E Y W O R D S allergen-specific immunotherapy, blocking antibodies, clinical trial, efficacy, hypoallergenic, recombinant derivatives, safety, Treg Present AIT Delivery route SCIT SLIT Molecules Allergen extracts +/-Adjuvant Alum 26Abbreviations: 8x6Q2W, grass allergen peptides at 6 nmol at 2-wk intervals for a total of 8

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Intralymphatic Immunotherapy: Update and Unmet Needs

Cited by 84 publications

References 33 publications

30 years of sublingual immunotherapy

30 years of sublingual immunotherapy

Diverse Mechanisms of Allergen Specific Immunotherapy

Molecular approaches to allergen‐specific immunotherapy: Are we so far from clinical implementation?

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