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    Codelivery of antigen and an immune cell adhesion inhibitor is necessary for efficacy of soluble antigen arrays in experimental autoimmune encephalomyelitis

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    Issue Date
    2014-04
    Author
    Sestak, Joshua
    Sullivan, Bradley P.
    Thati, Shara
    Northrup, Laura Ann
    Hartwell, Brittany
    Antunez, Lorena
    Forrest, M. Laird
    Vines, Charlotte M.
    Siahaan, Teruna J.
    Berkland, Cory J.
    Publisher
    Nature Publishing Group
    Type
    Article
    Article Version
    Scholarly/refereed, publisher version
    Metadata
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    Abstract
    Autoimmune diseases such as multiple sclerosis (MS) are typified by the misrecognition of self-antigen and the clonal expansion of autoreactive T cells. Antigen-specific immunotherapies (antigen-SITs) have long been explored as a means to desensitize patients to offending self-antigen(s) with the potential to retolerize the immune response. Soluble antigen arrays (SAgAs) are composed of hyaluronic acid (HA) cografted with disease-specific autoantigen (proteolipid protein peptide) and an ICAM-1 inhibitor peptide (LABL). SAgAs were designed as an antigen-SIT that codeliver peptides to suppress experimental autoimmune encephalomyelitis (EAE), a murine model of MS. Codelivery of antigen and cell adhesion inhibitor (LABL) conjugated to HA was essential for SAgA treatment of EAE. Individual SAgA components or mixtures thereof reduced proinflammatory cytokines in cultured splenocytes from EAE mice; however, these treatments showed minimal to no in vivo therapeutic effect in EAE mice. Thus, carriers that codeliver antigen and a secondary “context” signal (e.g., LABL) in vivo may be an important design criteria to consider when designing antigen-SIT for autoimmune therapy.
    Description
    This is the published version. Copyright 2014 Nature Publishing Group.
    URI
    http://hdl.handle.net/1808/18505
    DOI
    https://doi.org/10.1038/mtm.2014.8
    Collections
    • Bioengineering Program Scholarly Works [144]
    • Pharmaceutical Chemistry Scholarly Works [336]
    Citation
    Sestak, Joshua O., Bradley P. Sullivan, Sharadvi Thati, Laura Northrup, Brittany Hartwell, Lorena Antunez, M. Laird Forrest, Charlotte M. Vines, Teruna J. Siahaan, and Cory Berkland. "Codelivery of Antigen and an Immune Cell Adhesion Inhibitor Is Necessary for Efficacy of Soluble Antigen Arrays in Experimental Autoimmune Encephalomyelitis." Molecular Therapy — Methods & Clinical Development Mol Ther Methods Clin Dev 1 (2014): 14008. doi: 10.1038/mtm.2014.8.

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    Contact KU ScholarWorks
    785-864-8983
    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    785-864-8983

    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    Image Credits
     

     

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