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      International Journal of Nanomedicine (submit here)

      This international, peer-reviewed Open Access journal by Dove Medical Press focuses on the application of nanotechnology in diagnostics, therapeutics, and drug delivery systems throughout the biomedical field. Sign up for email alerts here.

      105,621 Monthly downloads/views I 7.033 Impact Factor I 10.9 CiteScore I 1.22 Source Normalized Impact per Paper (SNIP) I 1.032 Scimago Journal & Country Rank (SJR)

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      Co-delivery of allergen epitope fragments and R848 inhibits food allergy by inducing tolerogenic dendritic cells and regulatory T cells

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          Abstract

          Background

          Food allergy (FA) is a significant public health problem. The therapeutic efficacy for FA is unsatisfactory currently. The breakdown of intestinal immune tolerance is associated with the pathogenesis of FA. Therefore, it is of great significance to develop novel therapeutic methods to restore immune tolerance in treating FA.

          Methods

          We proposed an oral administration strategy to treat FA by co-delivering food allergen epitope fragment (peptide: IK) and adjuvant R848 (TLR7 ligand) in the mPEG–PDLLA nanoparticles (PPLA-IK/R848 NPs). The generation of tolerogenic dendritic cells (DCs) and regulatory T cells (Tregs) induced by PPLA-IK/R848 NPs were evaluated in vitro and in vivo. The therapeutic effects of PPLA-IK/R848 NPs were also assessed in an OVA-induced FA model.

          Results

          PPLA-IK/R848 NPs could efficiently deliver IK to DCs to drive DCs into the tolerogenic phenotypes and promote the differentiation of Tregs in vitro and in vivo, significantly inhibited FA responses through the recovery of intestinal immune tolerance.

          Conclusion

          Oral administration of PPLA-IK/R848 NPs could efficiently deliver IK and R848 to intestinal DCs and stimulate DCs into allergen tolerogenic phenotype. These tolerogenic DCs could promote the differentiation of Tregs, which significantly protected mice from food allergic responses. This study provided an efficient formulation to alleviate FA through the recovery of immune tolerance.

          Most cited references45

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          Oral druggable space beyond the rule of 5: insights from drugs and clinical candidates.

          Bradley Doak, Bjӧrn Over, Fabrizio Giordanetto … (2014)
          The rule of 5 (Ro5) is a set of in silico guidelines applied to drug discovery to prioritize compounds with an increased likelihood of high oral absorption. It has been influential in reducing attrition due to poor pharmacokinetics over the last 15 years. However, strict reliance on the Ro5 may have resulted in lost opportunities, particularly for difficult targets. To identify opportunities for oral drug discovery beyond the Ro5 (bRo5), we have comprehensively analyzed drugs and clinical candidates with molecular weight (MW) > 500 Da. We conclude that oral drugs are found far bRo5 and properties such as intramolecular hydrogen bonding, macrocyclization, dosage, and formulations can be used to improve bRo5 bioavailability. Natural products and structure-based design, often from peptidic leads, are key sources for oral bRo5 drugs. These insights should help guide the design of oral drugs in bRo5 space, which is of particular interest for difficult targets.
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            Epidemiology of food allergy.

            Scott H. Sicherer (2011)
            Adverse reactions to foods can occur for a variety of reasons, but a food allergy is caused by a specific immune response. Challenges to determine the prevalence of food allergy include misclassification, biased participation, lack of simple diagnostic tests, rapid evolution of disease, large numbers of potential triggers, and varied clinical phenotypes. Nonetheless, it is clear that this is a common disorder, with studies suggesting a cumulative prevalence of 3% to 6%, representing a significant impact on quality of life and costs. The inclusion of mild reactions to fruits and vegetables could result in calculation of prevalence exceeding 10% in some regions. There are data from numerous studies to suggest an increase in prevalence, but methodologic concerns warrant caution. Prevalence varies by age, geographic location, and possibly race/ethnicity. Many childhood food allergies resolve. Population-based epidemiologic studies have generated numerous novel theories regarding risks, including modifiable factors such as components of the maternal and infant diet, obesity, and the timing of food introduction. Recent and ongoing studies provide insights on risk factors, prevalence, and natural course that may inform clinical trials to improve diagnosis, prevention, and treatment. Copyright © 2011 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.
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              Induction of antigen-specific immunity with a vaccine targeting NY-ESO-1 to the dendritic cell receptor DEC-205.

              M. Dhodapkar, M Sznol, B. Zhao … (2014)
              Immune-based therapies for cancer are generating substantial interest because of the success of immune checkpoint inhibitors. This study aimed to enhance anticancer immunity by exploiting the capacity of dendritic cells (DCs) to initiate T cell immunity by efficient uptake and presentation of endocytosed material. Delivery of tumor-associated antigens to DCs using receptor-specific monoclonal antibodies (mAbs) in the presence of DC-activating agents elicits robust antigen-specific immune responses in preclinical models. DEC-205 (CD205), a molecule expressed on DCs, has been extensively studied for its role in antigen processing and presentation. CDX-1401 is a vaccine composed of a human mAb specific for DEC-205 fused to the full-length tumor antigen NY-ESO-1. This phase 1 trial assessed the safety, immunogenicity, and clinical activity of escalating doses of CDX-1401 with the Toll-like receptor (TLR) agonists resiquimod (TLR7/8) and Hiltonol (poly-ICLC, TLR3) in 45 patients with advanced malignancies refractory to available therapies. Treatment induced humoral and cellular immunity to NY-ESO-1 in patients with confirmed NY-ESO-1-expressing tumors across various dose levels and adjuvant combinations. No dose-limiting or grade 3 toxicities were reported. Thirteen patients experienced stabilization of disease, with a median duration of 6.7 months (range, 2.4+ to 13.4 months). Two patients had tumor regression (~20% shrinkage in target lesions). Six of eight patients who received immune-checkpoint inhibitors within 3 months after CDX-1401 administration had objective tumor regression. This first-in-human study of a protein vaccine targeting DCs demonstrates its feasibility, safety, and biological activity and provides rationale for combination immunotherapy strategies including immune checkpoint blockade.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Int J Nanomedicine
                Journal ID (iso-abbrev): Int J Nanomedicine
                Journal ID (publisher-id): IJN
                Journal ID (pmc): intjnano
                Title: International Journal of Nanomedicine
                Publisher: Dove
                ISSN (Print): 1176-9114
                ISSN (Electronic): 1178-2013
                Publication date (Electronic): 30 August 2019
                Publication date Collection: 2019
                Volume: 14
                Pages: 7053-7064
                Affiliations
                [1 ]Department of Allergy, The Third Affiliated Hospital of Shenzhen University , Shenzhen 518020, People’s Republic of China
                [2 ]Research Center of Allergy & Immunology, Department of Medicine, Shenzhen University , Shenzhen 518055, People’s Republic of China
                [3 ]State Key Laboratory of Respiratory Disease, Department of Allergy and Clinical Immunology, Guangzhou Medical University , Guangzhou 510006, People’s Republic of China
                Author notes
                Correspondence: Pixin Ran State Key Laboratory of Respiratory Disease, Department of Allergy and Clinical Immunology, Guangzhou Medical University, Jingxiu Road, Xinzao, Panyu District , Shenzhen510006, People’s Republic of ChinaTel +86 20 3710 3099Fax +86 20 3710 3099Email pxran@vip.163.com
                Pingchang YangResearch Center of Allergy & Immunology,Department of Medicine, Shenzhen University, Room A7-509 at Xili Campus, 1066 Xueyuan Blvd , Shenzhen518055, People’s Republic of ChinaTel +86 755 8617 2722Fax +86 755 8667 1906 Email pcy2356@szu.edu.cn
                [*]

                These authors contributed equally to this work

                Article
                Publisher ID: 215415
                DOI: 10.2147/IJN.S215415
                PMC ID: 6722440
                PubMed ID: 31564865
                SO-VID: 8dbca551-21e5-4861-b781-115ea35b7f11
                Copyright © © 2019 Hong et al.
                License:

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                History
                Date received : 12 May 2019
                Date accepted : 29 July 2019
                Page count
                Figures: 5, References: 54, Pages: 12
                Categories
                Subject: Original Research

                ScienceOpen disciplines: Molecular medicine
                Keywords: food allergy,co-delivery,allergen epitope fragment,r848,dendritic cells,tregs
                Data availability:
                ScienceOpen disciplines: Molecular medicine
                Keywords: food allergy, co-delivery, allergen epitope fragment, r848, dendritic cells, tregs

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