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    Antigen-Drug Conjugates as a Novel Therapeutic Class for the Treatment of Antigen-Specific Autoimmune Disorders

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    Pickens_2020.pdf (1.877Mb)
    Issue Date
    2019-05-14
    Author
    Pickens, Chad J.
    Christopher, Matthew A.
    Leon, Martin A.
    Pressnall, Melissa M.
    Johnson, Stephanie N.
    Thati, Sharadvi
    Sullivan, Bradley P.
    Berkland, Cory
    Publisher
    American Chemical Society
    Type
    Article
    Article Version
    Scholarly/refereed, author accepted manuscript
    Rights
    Copyright © 2019 American Chemical Society
    Metadata
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    Abstract
    Multiple sclerosis represents the world’s most common cause of neurological disability in young people and is attributed to a loss of immune tolerance toward proteins of the myelin sheath. Typical treatment options for MS patients involve immunomodulatory drugs, which act non-specifically, resulting in global immunosuppression. The study discussed herein aims to demonstrate the efficacy of antigen-specific immunotherapies involving conjugation of disease causing auto-antigen, PLP139–151, and a potent immunosuppressant, dexamethasone. Antigen-drug conjugates (AgDCs) were formed using copper-catalyzed azide-alkyne cycloaddition chemistry with the inclusion of a hydrolyzable linker to maintain activity of released dexamethasone. Subcutaneous administration of this antigen-drug conjugate to SJL mice induced with experimental autoimmune encephalomyelitis protected the mice from symptom onset throughout the 25-day study, demonstrating enhanced efficacy in comparison to dexamethasone treatment. These results highlight the benefits of co-delivery of auto-antigens with immunosuppressant drugs as AgDCs for the treatment of autoimmune diseases.
    Description
    This document is the Accepted Manuscript version of a Published Work that appeared in final form in Molecular Pharmaceutics, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see doi.org/10.1021/acs.molpharmaceut.9b00063.
    URI
    http://hdl.handle.net/1808/30978
    DOI
    https://doi.org/10.1021/acs.molpharmaceut.9b00063
    Collections
    • Pharmaceutical Chemistry Scholarly Works [336]
    Citation
    Pickens, C. J., Christopher, M. A., Leon, M. A., Pressnall, M. M., Johnson, S. N., Thati, S., Sullivan, B. P., & Berkland, C. (2019). Antigen-Drug Conjugates as a Novel Therapeutic Class for the Treatment of Antigen-Specific Autoimmune Disorders. Molecular pharmaceutics, 16(6), 2452–2461. https://doi.org/10.1021/acs.molpharmaceut.9b00063

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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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