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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
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.
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.
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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.
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This is the published version. Copyright 2014 Nature Publishing Group.
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2014-04
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Nature Publishing Group
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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.